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Exploring neuroglial signaling: diversity of molecules implicated in microglia-to-astrocyte neuroimmune communication

  • Zainab B. Mohammad , Samantha C. Y. Yudin , Benjamin J. Goldberg , Kursti L. Serra and Andis Klegeris ORCID logo EMAIL logo
Published/Copyright: September 3, 2024
Become an author with De Gruyter Brill

Abstract

Effective communication between different cell types is essential for brain health, and dysregulation of this process leads to neuropathologies. Brain glial cells, including microglia and astrocytes, orchestrate immune defense and neuroimmune responses under pathological conditions during which interglial communication is indispensable. Our appreciation of the complexity of these processes is rapidly increasing due to recent advances in molecular biology techniques, which have identified numerous phenotypic states of both microglia and astrocytes. This review focuses on microglia-to-astrocyte communication facilitated by secreted neuroimmune modulators. The combinations of interleukin (IL)-1α, tumor necrosis factor (TNF), plus complement component C1q as well as IL-1β plus TNF are already well-established microglia-derived stimuli that induce reactive phenotypes in astrocytes. However, given the large number of inflammatory mediators secreted by microglia and the rapidly increasing number of distinct functional states recognized in astrocytes, it can be hypothesized that many more intercellular signaling molecules exist. This review identifies the following group of cytokines and gliotransmitters that, while not established as interglial mediators yet, are known to be released by microglia and elicit functional responses in astrocytes: IL-10, IL-12, IL-18, transforming growth factor (TGF)-β, interferon (IFN)-γ, C–C motif chemokine ligand (CCL)5, adenosine triphosphate (ATP), l-glutamate, and prostaglandin E2 (PGE2). The review of molecular mechanisms engaged by these mediators reveals complex, partially overlapping signaling pathways implicated in numerous neuropathologies. Additionally, lack of human-specific studies is identified as a significant knowledge gap. Further research on microglia-to-astrocyte communication is warranted, as it could discover novel interglial signaling-targeted therapies for diverse neurological disorders.


Corresponding author: Andis Klegeris, Laboratory of Cellular and Molecular Pharmacology, Department of Biology, University of British Columbia Okanagan Campus, Kelowna, BC, V1V 1V7, Canada, E-mail:
Zainab B. Mohammad and Samantha C. Y. Yudin contributed equally to this work.

Funding source: Jack Brown and Family Alzheimer Disease Research Foundation

Acknowledgments

The authors would like to thank all members of the Laboratory of Cellular and Molecular Pharmacology for the helpful discussions and comments on the manuscript.

  1. Research ethics: Not applicable.

  2. Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: The authors state no conflict of interest.

  4. Research funding: This research was supported by grants from the Jack Brown and Family Alzheimer’s Disease Research Foundation, the Natural Sciences and Engineering Research Council of Canada, and the University of British Columbia Okanagan Campus.

  5. Data availability: Not applicable.

References

Abbracchio, M.P. and Ceruti, S. (2006). Roles of P2 receptors in glial cells: focus on astrocytes. Purinergic Signal. 2: 595–604, https://doi.org/10.1007/s11302-006-9016-0.Search in Google Scholar PubMed PubMed Central

Abramov, A.Y., Jacobson, J., Wientjes, F., Hothersall, J., Canevari, L., and Duchen, M.R. (2005). Expression and modulation of an NADPH oxidase in mammalian astrocytes. J. Neurosci. 25: 9176–9184, https://doi.org/10.1523/jneurosci.1632-05.2005.Search in Google Scholar

Ali, M.M., Ghouri, R.G., Ans, A.H., Akbar, A., and Toheed, A. (2019). Recommendations for anti-inflammatory treatments in Alzheimer’s disease: a comprehensive review of the literature. Cureus 11: e4620, https://doi.org/10.7759/cureus.4620.Search in Google Scholar PubMed PubMed Central

Aloisi, F., Penna, G., Cerase, J., Iglesias, B.M., and Adorini, L. (1997). IL-12 production by central nervous system microglia is inhibited by astrocytes. J. Immunol. 159: 1604–1612, https://doi.org/10.4049/jimmunol.159.4.1604.Search in Google Scholar

Andreadou, M., Ingelfinger, F., De Feo, D., Cramer, T.L.M., Tuzlak, S., Friebel, E., Schreiner, B., Eede, P., Schneeberger, S., Geesdorf, M., et al.. (2023). IL-12 sensing in neurons induces neuroprotective CNS tissue adaptation and attenuates neuroinflammation in mice. Nat. Neurosci. 26: 1701–1712, https://doi.org/10.1038/s41593-023-01435-z.Search in Google Scholar PubMed PubMed Central

Andreasson, K. (2010). Emerging roles of PGE2 receptors in models of neurological disease. Prostag. Other Lipid Mediat. 91: 104–112, https://doi.org/10.1016/j.prostaglandins.2009.04.003.Search in Google Scholar PubMed PubMed Central

Appay, V. and Rowland-Jones, S.L. (2001). CCL5: a versatile and controversial chemokine. Trends Immunol. 22: 83–87, https://doi.org/10.1016/s1471-4906(00)01812-3.Search in Google Scholar PubMed

Arany, I., Tyring, S.K., Brysk, H., and Brysk, M.M. (1998). Induction by interferon-γ of its receptor varies with epithelial differentiation and cell type. Arch. Dermatol. Res. 290: 331–334, https://doi.org/10.1007/s004030050313.Search in Google Scholar PubMed

Armada-Moreira, A., Gomes, J.I., Pina, C.C., Savchak, O.K., Gonçalves-Ribeiro, J., Rei, N., Pinto, S., Morais, T.P., Martins, R.S., Ribeiro, F.F., et al.. (2020). Going the extra (synaptic) mile: excitotoxicity as the road toward neurodegenerative diseases. Front. Cell. Neurosci. 14: 90, https://doi.org/10.3389/fncel.2020.00090.Search in Google Scholar PubMed PubMed Central

Bai, K., Chuang, K., Chen, C., Jhan, M., Hsiao, T., Cheng, T., Chang, L., Chang, T., and Chuang, H. (2019). Microglial activation and inflammation caused by traffic-related particulate matter. Chem. Biol. Interact. 311: 108762, https://doi.org/10.1016/j.cbi.2019.108762.Search in Google Scholar PubMed

Balak, C., Han, C.Z., and Glass, C.K. (2024). Deciphering microglia phenotypes in health and disease. Curr. Opin. Genet. Dev. 84: 102146, https://doi.org/10.1016/j.gde.2023.102146.Search in Google Scholar PubMed

Balasingam, V. and Yong, V.W. (1996). Attenuation of astroglial reactivity by interleukin-10. J. Neurosci. 16: 2945–2955, https://doi.org/10.1523/jneurosci.16-09-02945.1996.Search in Google Scholar PubMed PubMed Central

Barnes, D.A., Huston, M., Holmes, R., Benveniste, E.N., Yong, V.W., Scholz, P., and Perez, H.D. (1996). Induction of CCL5 expression by astrocytes and astrocytoma cell lines. J. Neuroimmunol. 71: 207–214, https://doi.org/10.1016/s0165-5728(96)00154-3.Search in Google Scholar PubMed

Bartels, A.L. and Leenders, K.L. (2010). Cyclooxygenase and neuroinflammation in Parkinson’s disease neurodegeneration. Curr. Neuropharmacol. 8: 62–68, https://doi.org/10.2174/157015910790909485.Search in Google Scholar PubMed PubMed Central

Becher, B., Dodelet, V., Fedorowicz, V., and Antel, J.P. (1996). Soluble tumor necrosis factor receptor inhibits interleukin 12 production by stimulated human adult microglial cells in vitro. J. Clin. Invest. 98: 1539–1543, https://doi.org/10.1172/jci118946.Search in Google Scholar

Bernath, A.K., Murray, T.E., Yang, S., Gibon, J., and Klegeris, A. (2023). Microglia secrete distinct sets of neurotoxins in a stimulus-dependent manner. Brain Res. 1807: 148315, https://doi.org/10.1016/j.brainres.2023.148315.Search in Google Scholar PubMed

Bernaus, A., Blanco, S., and Sevilla, A. (2020). Glia crosstalk in neuroinflammatory diseases. Front. Cell. Neurosci. 14: 539179, https://doi.org/10.3389/fncel.2020.00209.Search in Google Scholar PubMed PubMed Central

Bhat, P., Leggatt, G.R., Waterhouse, N.J., and Frazer, I.H. (2017). Interferon-γ derived from cytotoxic lymphocytes directly enhances their motility and cytotoxicity. Cell Death Dis. 8: e2836, https://doi.org/10.1038/cddis.2017.67.Search in Google Scholar PubMed PubMed Central

Bianco, F., Pravettoni, E., Colombo, A., Schenk, U., Möller, T., Matteoli, M., and Verderio, C. (2005). Astrocyte-derived ATP induces vesicle shedding and IL-1 beta release from microglia. J. Immunol. 174: 7268–7277, https://doi.org/10.4049/jimmunol.174.11.7268.Search in Google Scholar PubMed

Böhmwald, K., Andrade, C.A., and Kalergis, A.M. (2021). Contribution of pro-inflammatory molecules induced by respiratory virus infections to neurological disorders. Pharmaceuticals 14: 340, https://doi.org/10.3390/ph14040340.Search in Google Scholar PubMed PubMed Central

Bonora, M., Patergnani, S., Rimessi, A., Marchi, E.D., Suski, J.M., Bononi, A., Giorgi, C., Marchi, S., Missiroli, S., Poletti, F., et al.. (2012). ATP synthesis and storage. Purinergic Signal. 8: 343–357, https://doi.org/10.1007/s11302-012-9305-8.Search in Google Scholar PubMed PubMed Central

Brambilla, R., Bracchi-Ricard, V., Hu, W., Frydel, B.R., Bramwell, A., Karmally, S., Green, E.J., and Bethea, J.R. (2005). Inhibition of astroglial nuclear factor κB reduces inflammation and improves functional recovery after spinal cord injury. J. Exp. Med. 202: 145–156, https://doi.org/10.1084/jem.20041918.Search in Google Scholar PubMed PubMed Central

Bruzzone, S., Verderio, C., Schenk, U., Fedele, E., Zocchi, E., Matteoli, M., and Flora, A.D. (2004). Glutamate-mediated overexpression of CD38 in astrocytes cultured with neurones. J. Neurochem. 89: 264–272, https://doi.org/10.1111/j.1471-4159.2003.02326.x.Search in Google Scholar PubMed

Bukke, V.N., Archana, M., Villani, R., Romano, A.D., Wawrzyniak, A., Balawender, K., Orkisz, S., Beggiato, S., Serviddio, G., and Cassano, T. (2020). The dual role of glutamatergic neurotransmission in Alzheimer’s disease: from pathophysiology to pharmacotherapy. Int. J. Mol. Sci. 21: 7452, https://doi.org/10.3390/ijms21207452.Search in Google Scholar PubMed PubMed Central

Burmeister, A.R. and Marriott, I. (2018). The interleukin-10 family of cytokines and their role in the CNS. Front. Cell. Neurosci. 12: 458, https://doi.org/10.3389/fncel.2018.00458.Search in Google Scholar PubMed PubMed Central

Bustamante-Barrientos, F.A., Luque-Campos, N., Araya, M.J., Lara-Barba, E., de Solminihac, J., Pradenas, C., Molina, L., Herrera-Luna, Y., Utreras-Mendoza, Y., Elizondo-Vega, R., et al.. (2023). Mitochondrial dysfunction in neurodegenerative disorders: potential therapeutic application of mitochondrial transfer to central nervous system-residing cells. J. Transl. Med. 21: 613, https://doi.org/10.1186/s12967-023-04493-w.Search in Google Scholar PubMed PubMed Central

Cartier, L., Hartley, O., Dubois-Dauphin, M., and Krause, K.H. (2005). Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases. Brain Res. Rev. 48: 16–42, https://doi.org/10.1016/j.brainresrev.2004.07.021.Search in Google Scholar PubMed

Cekanaviciute, E., Fathali, N., Doyle, K.P., Williams, A.M., Han, J., and Buckwalter, M.S. (2014). Astrocytic transforming growth factor-beta signaling reduces subacute neuroinflammation after stroke in mice. Glia 62: 1227–1240, https://doi.org/10.1002/glia.22675.Search in Google Scholar PubMed PubMed Central

Chai, H., Díaz-Castro, B., Shigetomi, E., Monte, E., Octeau, J.C., Yu, X., Cohn, W., Rajendran, P.S., Vondriska, T.M., Whitelegge, J.P., et al.. (2017). Neural circuit-specialized astrocytes: transcriptomic, proteomic, morphological, and functional evidence. Neuron 95: 531–549.e9, https://doi.org/10.1016/j.neuron.2017.06.029.Search in Google Scholar PubMed PubMed Central

Chen, H., Hu, B., Lv, X., Zhu, S., Zhen, G., Wan, M., Jain, A., Gao, B., Chai, Y., Yang, M., et al.. (2019). Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis. Nat. Commun. 10: 1–13, https://doi.org/10.1038/s41467-018-08097-7.Search in Google Scholar PubMed PubMed Central

Chen, H., Sung, F., Oyarzabal, E.A., Tan, M., Leonard, J., Guo, M., Li, S., Wang, Q., Chu, H., Chen, L., et al.. (2018). Physiological concentration of prostaglandin E2 exerts anti-inflammatory effects by inhibiting microglial production of superoxide through a novel pathway. Mol. Neurobiol. 55: 8001–8013, https://doi.org/10.1007/s12035-018-0965-4.Search in Google Scholar PubMed PubMed Central

Chen, H.B., Chan, T., Hung, A.C., Tsai, C., and Sun, S.H. (2006). Elucidation of ATP-stimulated stress protein expression of RBA-2 type-2 astrocytes: ATP potentiate HSP60 and Cu/Zn SOD expression and stimulates pI shift of peroxiredoxin II. J. Cell. Biochem. 97: 314–326, https://doi.org/10.1002/jcb.20547.Search in Google Scholar PubMed

Chen, J., Tsai, C., Lin, H., Huang, C., Leung, Y., Lai, S., Tsai, C., Chang, P., Lu, D., and Lin, C. (2015). Interlukin-18 is a pivot regulatory factor on matrix metalloproteinase-13 expression and brain astrocytic migration. Mol. Neurobiol. 53: 6218–6227, https://doi.org/10.1007/s12035-015-9529-z.Search in Google Scholar PubMed

Cheng, H., Huang, H., Guo, Z., Chang, Y., and Li, Z. (2021). Role of prostaglandin E2 in tissue repair and regeneration. Theranostics 11: 8836–8854, https://doi.org/10.7150/thno.63396.Search in Google Scholar PubMed PubMed Central

Cho, C.E., Damle, S., Wancewicz, E.V., Mukhopadhyay, S., Hart, C.E., Mazur, C., Swayze, E.E., and Kamme, F. (2019). A modular analysis of microglia gene expression, insights into the aged phenotype. BMC Genomics 20: 164, https://doi.org/10.1186/s12864-019-5549-9.Search in Google Scholar PubMed PubMed Central

Choi, S.S., Lee, H.J., Lim, I., and Kim, S.U. (2014). Human astrocytes: secretome profiles of cytokines and chemokines. PLoS One 9: e92325, https://doi.org/10.1371/journal.pone.0092325.Search in Google Scholar PubMed PubMed Central

Clasadonte, J., Poulain, P., Hanchate, N.K., Corfas, G., Ojeda, S.R., and Prevot, V. (2011). Prostaglandin E2 release from astrocytes triggers gonadotropin-releasing hormone (GnRH) neuron firing via EP2 receptor activation. Proc. Natl. Acad. Sci. U. S. A. 108: 16104–16109, https://doi.org/10.1073/pnas.1107533108.Search in Google Scholar PubMed PubMed Central

Conti, B., Park, L.C., Calingasan, N.Y., Kim, Y., Kim, H., Bae, Y., Gibson, G.E., and Joh, T.H. (1999). Cultures of astrocytes and microglia express interleukin 18. Mol. Brain Res. 67: 46–52, https://doi.org/10.1016/s0169-328x(99)00034-0.Search in Google Scholar PubMed

Coomey, R., Stowell, R., Majewska, A., and Tropea, D. (2020). The role of microglia in neurodevelopmental disorders and their therapeutics. Curr. Top. Med. Chem. 20: 272–276, https://doi.org/10.2174/1568026620666200221172619.Search in Google Scholar PubMed PubMed Central

Cuní-López, C., Stewart, R., Quek, H., and White, A.R. (2022). Recent advances in microglia modelling to address translational outcomes in neurodegenerative diseases. Cells 11: 1662, https://doi.org/10.3390/cells11101662.Search in Google Scholar PubMed PubMed Central

Cunningham, C., Dunne, A., and López-Rodríguez, A.B. (2018). Astrocytes: heterogeneous and dynamic phenotypes in neurodegeneration and innate immunity. Neuroscientist 25: 455–474, https://doi.org/10.1177/1073858418809941.Search in Google Scholar PubMed PubMed Central

Danbolt, N.C. (2001). Glutamate uptake. Prog. Neurobiol. 65: 1–105, https://doi.org/10.1016/s0301-0082(00)00067-8.Search in Google Scholar PubMed

De Freitas, M.S., Spohr, T.C.L.S., Benedito, A.B., Caetano, M.S., Margulis, B.A., Lopes, U.G., and Moura‐Neto, V. (2002). Neurite outgrowth is impaired on HSP70-positive astrocytes through a mechanism that requires NF-κB activation. Brain Res. 958: 359–370, https://doi.org/10.1016/s0006-8993(02)03682-x.Search in Google Scholar PubMed

Dey, I., Lejeune, M., and Chadee, K. (2006). Prostaglandin E2 receptor distribution and function in the gastrointestinal tract. Br. J. Pharmacol. 149: 611–623, https://doi.org/10.1038/sj.bjp.0706923.Search in Google Scholar PubMed PubMed Central

Dinarello, C.A. (1999). IL-18: a TH1 -inducing, proinflammatory cytokine and new member of the IL-1 family. J. Allergy Clin. Immunol. 103: 11–24, https://doi.org/10.1016/s0091-6749(99)70518-x.Search in Google Scholar PubMed

Dinarello, C.A. and Fantuzzi, G. (2003). Interleukin‐18 and host defense against infection. J. Infect. Dis. 187: S370–S384, https://doi.org/10.1086/374751.Search in Google Scholar PubMed

Ding, X., Yan, Y., Li, X., Li, K., Ciric, B., Yang, J., Zhang, Y., Wu, S., Xu, H., Chen, W., et al.. (2015). Silencing IFN-γ binding/signaling in astrocytes versus microglia leads to opposite effects on central nervous system autoimmunity. J. Immunol. 194: 4251–4264, https://doi.org/10.4049/jimmunol.1303321.Search in Google Scholar PubMed PubMed Central

Diniz, L.P., Almeida, J., Tortelli, V., Lopes, C.V., Setti-Perdigão, P., Stipursky, J., Kahn, S.A., Romão, L., De Miranda, J., Alves-Leon, S.V., et al.. (2012). Astrocyte-induced synaptogenesis is mediated by transforming growth factor β signaling through modulation of d-serine levels in cerebral cortex neurons. J. Biol. Chem. 287: 41432–41445, https://doi.org/10.1074/jbc.m112.380824.Search in Google Scholar PubMed PubMed Central

Domercq, M., Brambilla, L., Pilati, E., Marchaland, J., Volterra, A., and Bezzi, P. (2006). P2Y1 receptor-evoked glutamate exocytosis from astrocytes: control by tumor necrosis factor-α and prostaglandins. J. Biol. Chem. 281: 30684–30696, https://doi.org/10.1074/jbc.m606429200.Search in Google Scholar PubMed

Dou, Y., Wu, H., Li, H., Qin, S., Wang, Y., Li, J., Lou, H., Chen, Z., Li, X., Luo, Q., et al.. (2012). Microglial migration mediated by ATP-induced ATP release from lysosomes. Cell Res. 22: 1022–1033, https://doi.org/10.1038/cr.2012.10.Search in Google Scholar PubMed PubMed Central

Dutta, G., Zhang, P., and Liu, B. (2008). The lipopolysaccharide Parkinson’s disease animal model: mechanistic studies and drug discovery. Fundam. Clin. Pharmacol. 22: 453–464, https://doi.org/10.1111/j.1472-8206.2008.00616.x.Search in Google Scholar

Escartin, C., Galea, E., Lakatos, A., O’Callaghan, J.P., Petzold, G.C., Serrano-Pozo, A., Steinhäuser, C., Volterra, A., Carmignoto, G., Agarwal, A., et al.. (2021). Reactive astrocyte nomenclature, definitions, and future directions. Nat. Neurosci. 24: 312–325, https://doi.org/10.1038/s41593-020-00783-4.Search in Google Scholar

Falcone, C. (2022). Evolution of astrocytes: from invertebrates to vertebrates. Front. Cell Dev. Biol. 10: 931311, https://doi.org/10.3389/fcell.2022.931311.Search in Google Scholar

Fan, D., Grooms, S.Y., Araneda, R.C., Johnson, A.B., Dobrenis, K., Kessler, J.A., and Zukin, R.S. (1999). AMPA receptor protein expression and function in astrocytes cultured from hippocampus. J. Neurosci. Res. 57: 557–571, https://doi.org/10.1002/(sici)1097-4547(19990815)57:4<557::aid-jnr16>3.3.co;2-9.10.1002/(SICI)1097-4547(19990815)57:4<557::AID-JNR16>3.3.CO;2-9Search in Google Scholar

Festa, B.P., Siddiqi, F.H., Jimenez-Sanchez, M., Won, H., Rob, M., Djajadikerta, A., Stamatakou, E., and Rubinsztein, D.C. (2023). Microglial-to-neuronal CCR5 signaling regulates autophagy in neurodegeneration. Neuron 111: 2021–2037.e12, https://doi.org/10.1016/j.neuron.2023.04.006.Search in Google Scholar

Fiebich, B.L., Schleicher, S., Spleiss, O., Czygan, M., and Hüll, M. (2001). Mechanisms of prostaglandin E2-induced interleukin-6 release in astrocytes: possible involvement of EP4-like receptors, p38 mitogen-activated protein kinase and protein kinase C. J. Neurochem. 79: 950–958, https://doi.org/10.1046/j.1471-4159.2001.00652.x.Search in Google Scholar

Fitz, J.G. (2006). Regulation of cellular Atp release. Trans. Am. Clin. Climatol. Assoc. 118: 199–208.Search in Google Scholar

Flynn, G., Maru, S., Loughlin, J., Romero, I.A., and Male, D. (2003). Regulation of chemokine receptor expression in human microglia and astrocytes. J. Neuroimmunol. 136: 84–93, https://doi.org/10.1016/s0165-5728(03)00009-2.Search in Google Scholar

Freitag, K., Eede, P., Ivanov, A., Sterczyk, N., Schneeberger, S., Borodina, T., Sauer, S., Beule, D., and Heppner, F.L. (2023). Diverse but unique astrocytic phenotypes during embryonic stem cell differentiation, culturing and development. Commun. Biol. 6: 40, https://doi.org/10.1038/s42003-023-04410-3.Search in Google Scholar

Fujikawa, R. and Tsuda, M. (2023). The functions and phenotypes of microglia in Alzheimer’s disease. Cells 12: 1207, https://doi.org/10.3390/cells12081207.Search in Google Scholar

Gabay, C., Fautrel, B., Rech, J., Spertini, F., Feist, E., Kötter, I., Hachulla, E., Morel, J., Schaeverbeke, T., Hamidou, M., et al.. (2018). Open-label, multicentre, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still’s disease. Ann. Rheum. Dis. 77: 840–847, https://doi.org/10.1136/annrheumdis-2017-212608.Search in Google Scholar

Gao, C., Jiang, J., Tan, Y., and Chen, S. (2023). Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets. Signal Transduct. Target. Ther. 8: 359, https://doi.org/10.1038/s41392-023-01588-0.Search in Google Scholar PubMed PubMed Central

Garland, E.F., Hartnell, I.J., and Boche, D. (2022). Microglia and astrocyte function and communication: what do we know in humans? Front. Neurosci. 16: 824888, https://doi.org/10.3389/fnins.2022.824888.Search in Google Scholar PubMed PubMed Central

Garrido-Gil, P., Pedrosa, M.A., Garcia-Garrote, M., Pequeño-Valtierra, A., Rodríguez-Castro, J., García-Souto, D., Rodríguez-Pérez, A.I., and Labandeira-Garcia, J.L. (2022). Microglial angiotensin type 2 receptors mediate sex-specific expression of inflammatory cytokines independently of circulating estrogen. Glia 70: 2348–2360, https://doi.org/10.1002/glia.24255.Search in Google Scholar PubMed PubMed Central

Gebicke-Haerter, P.J., Schobert, A., Dieter, P., Honegger, P., and Hertting, G. (1991). Regulation and glucocorticoid-independent induction of lipocortin I in cultured astrocytes. J. Neurochem. 57: 175–183, https://doi.org/10.1111/j.1471-4159.1991.tb02113.x.Search in Google Scholar PubMed

Geirsdottir, L., David, E., Keren-Shaul, H., Weiner, A., Bohlen, S.C., Neuber, J., Balic, A., Giladi, A., Sheban, F., Dutertre, C.-A., et al.. (2019). Cross-species single-cell analysis reveals divergence of the primate microglia program. Cell 179: 1609–1622.e16, https://doi.org/10.1016/j.cell.2019.11.010.Search in Google Scholar PubMed

Giovannoni, F. and Quintana, F.J. (2020). The role of astrocytes in CNS inflammation. Trends Immunol. 41: 805–819, https://doi.org/10.1016/j.it.2020.07.007.Search in Google Scholar PubMed PubMed Central

Gong, Q., Lin, Y., Lu, Z., and Xiao, Z. (2020). Microglia-astrocyte cross talk through IL-18/IL-18R signaling modulates migraine-like behavior in experimental models of migraine. Neuroscience 451: 207–215, https://doi.org/10.1016/j.neuroscience.2020.10.019.Search in Google Scholar PubMed

Gordon, G.R., Choi, H.B., Rungta, R.L., Ellis-Davies, G.C., and MacVicar, B.A. (2008). Brain metabolism dictates the polarity of astrocyte control over arterioles. Nature 456: 745–749, https://doi.org/10.1038/nature07525.Search in Google Scholar PubMed PubMed Central

Gottlieb, A., Toledano-Furman, N.E., Prabhakara, K.S., Kumar, A., Caplan, H.W., Bedi, S.S., Cox, C.S., and Olson, S.D. (2022). Time dependent analysis of rat microglial surface markers in traumatic brain injury reveals dynamics of distinct cell subpopulations. Sci. Rep. 12: 6289, https://doi.org/10.1038/s41598-022-10419-1.Search in Google Scholar PubMed PubMed Central

Hashioka, S., Klegeris, A., Schwab, C., and McGeer, P.L. (2009). Interferon-γ-dependent cytotoxic activation of human astrocytes and astrocytoma cells. Neurobiol. Aging 30: 1924–1935, https://doi.org/10.1016/j.neurobiolaging.2008.02.019.Search in Google Scholar PubMed

Hattori, M. and Gouaux, E. (2012). Molecular mechanism of ATP binding and ion channel activation in P2X receptors. Nature 485: 207–212, https://doi.org/10.1038/nature11010.Search in Google Scholar PubMed PubMed Central

Henry, C.J., Huang, Y., Wynne, A.M., and Godbout, J.P. (2009). Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1beta and anti-inflammatory IL-10 cytokines. Brain Behav. Immun. 23: 309–317, https://doi.org/10.1016/j.bbi.2008.09.002.Search in Google Scholar PubMed PubMed Central

Hersh, J., Prah, J., Winters, A., Liu, R., and Yang, S.H. (2021). Modulation of astrocyte phenotype in response to T-cell interaction. J. Neuroimmunol. 351: 577455, https://doi.org/10.1016/j.jneuroim.2020.577455.Search in Google Scholar PubMed PubMed Central

Heufler, C., Koch, F., Stanzl, U., Topar, G., Wysocka, M., Trinchieri, G., Enk, A., Steinman, R.M., Romani, N., and Schuler, G. (1996). Interleukin-12 is produced by dendritic cells and mediates T helper 1 development as well as interferon-gamma production by T helper 1 cells. Eur. J. Immunol. 26: 659–668, https://doi.org/10.1002/eji.1830260323.Search in Google Scholar PubMed

Higashi, Y., Segawa, S., Matsuo, T., Nakamura, S., Kikkawa, Y., Nishida, K., and Nagasawa, K. (2011). Microglial zinc uptake via zinc transporters induces ATP release and the activation of microglia. Glia 59: 1933–1945, https://doi.org/10.1002/glia.21235.Search in Google Scholar PubMed

Höft, S., Griemsmann, S., Seifert, G., and Steinhäuser, C. (2014). Heterogeneity in expression of functional ionotropic glutamate and GABA receptors in astrocytes across brain regions: insights from the thalamus. Philos. Trans. R. Soc. Lond. B Biol. Sci. 369: 20130602, https://doi.org/10.1098/rstb.2013.0602.Search in Google Scholar PubMed PubMed Central

Hoozemans, J.J., Veerhuis, R., Janssen, I., Van Elk, E., Rozemuller, A.J., and Eikelenboom, P. (2002). The role of cyclo-oxygenase 1 and 2 activity in prostaglandin E2 secretion by cultured human adult microglia: implications for Alzheimer’s disease. Brain Res. 951: 218–226, https://doi.org/10.1016/s0006-8993(02)03164-5.Search in Google Scholar PubMed

Hu, S., Chao, C.C., Ehrlich, L.C., Sheng, W.S., Sutton, R.L., Rockswold, G.L., and Peterson, P.K. (1999). Inhibition of microglial cell CCL5 production by Il-10 and TGF-β. J. Leukoc. Biol. 65: 815–821, https://doi.org/10.1002/jlb.65.6.815.Search in Google Scholar PubMed

Hynd, M.R., Scott, H.L., and Dodd, P.R. (2004). Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer’s disease. Neurochem. Int. 45: 583–595, https://doi.org/10.1016/j.neuint.2004.03.007.Search in Google Scholar PubMed

Hyvärinen, T., Hagman, S., Ristola, M., Sukki, L., Veijula, K., Kreutzer, J., Kallio, P., and Narkilahti, S. (2019). Co-stimulation with IL-1β and TNF-α induces an inflammatory reactive astrocyte phenotype with neurosupportive characteristics in a human pluripotent stem cell model system. Sci. Rep. 9: 1–15, https://doi.org/10.1038/s41598-019-53414-9.Search in Google Scholar PubMed PubMed Central

Imura, Y., Morizawa, Y., Komatsu, R., Shibata, K., Shinozaki, Y., Kasai, H., Moriishi, K., Moriyama, Y., and Koizumi, S. (2013). Microglia release ATP by exocytosis. Glia 61: 1320–1330, https://doi.org/10.1002/glia.22517.Search in Google Scholar PubMed

Iwata, Y., Miyao, M., Hirotsu, A., Tatsumi, K., Matsuyama, T., Uetsuki, N., and Tanaka, T. (2021). The inhibitory effects of Orengedokuto on inducible PGE2 production in BV-2 microglial cells. Heliyon 7: e07759, https://doi.org/10.1016/j.heliyon.2021.e07759.Search in Google Scholar PubMed PubMed Central

Iyer, S.S. and Cheng, G. (2012). Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit. Rev. Immunol. 32: 23–63, https://doi.org/10.1615/critrevimmunol.v32.i1.30.Search in Google Scholar PubMed PubMed Central

Jana, M., Mondal, S., Jana, A., and Pahan, K. (2014). Interleukin-12 (IL-12), but not IL-23, induces the expression of IL-7 in microglia and macrophages: implications for multiple sclerosis. Immunology 141: 549–563, https://doi.org/10.1111/imm.12214.Search in Google Scholar PubMed PubMed Central

Jayasooriya, R., Moon, D.-O., Chol, Y., Yoon, C.-H., and Kim, G.-Y. (2011). Methanol extract of Hydroclathrus clathratus inhibits production of nitric oxide, prostaglandin E2 and tumor necrosis factor-α in lipopolysaccharide-stimulated BV2 microglial cells via inhibition of NF-κB activity. Trop. J. Pharm. Res. 10: 723–730, https://doi.org/10.4314/tjpr.v10i6.4.Search in Google Scholar

Jha, M.K., Jo, M., Kim, H., and Suk, K. (2018). Microglia-astrocyte crosstalk: an intimate molecular conversation. Neuroscientist 25: 227–240, https://doi.org/10.1177/1073858418783959.Search in Google Scholar PubMed

Jo, S., Kang, T., Koppula, S., Cho, D., Kim, J., Kim, I., and Choi, D. (2021). Mitigating effect of Lindera obtusiloba blume extract on neuroinflammation in microglial cells and scopolamine-induced amnesia in mice. Molecules 26: 2870, https://doi.org/10.3390/molecules26102870.Search in Google Scholar PubMed PubMed Central

Jurga, A.M., Paleczna, M., and Kuter, K. (2020). Overview of general and discriminating markers of differential microglia phenotypes. Front. Cell. Neurosci. 14: 198, https://doi.org/10.3389/fncel.2020.00198.Search in Google Scholar PubMed PubMed Central

Kawanokuchi, J., Mizuno, T., Takeuchi, H., Kato, H., Wang, J., Mitsuma, N., and Suzumura, A. (2006). Production of interferon-γ by microglia. Mult. Scler. J. 12: 558–564, https://doi.org/10.1177/1352458506070763.Search in Google Scholar PubMed

Kelder, W., McArthur, J.C., Nance‐Sproson, T., McClernon, D., and Griffin, D.E. (1998). Β‐chemokines MCP‐1 and rantes are selectively increased in cerebrospinal fluid of patients with human immunodeficiency virus–associated dementia. Ann. Neurol. 44: 831–835, https://doi.org/10.1002/ana.410440521.Search in Google Scholar PubMed

Kim, J., Yoo, I.D., Lim, J., and Moon, J. (2024). Pathological phenotypes of astrocytes in Alzheimer’s disease. Exp. Mol. Med. 56: 95–99, https://doi.org/10.1038/s12276-023-01148-0.Search in Google Scholar PubMed PubMed Central

Kim, S.Y., Moon, J.H., Lee, H.G., Kim, S.U., and Lee, Y.B. (2007). ATP released from β‐amyloid-stimulated microglia induces reactive oxygen species production in an autocrine fashion. Exp. Mol. Med. 39: 820–827, https://doi.org/10.1038/emm.2007.89.Search in Google Scholar PubMed

Kim, Y.H., Park, J., and Choi, Y.K. (2019). The role of astrocytes in the central nervous system focused on BK channel and heme oxygenase metabolites: a review. Antioxidants 8: 121, https://doi.org/10.3390/antiox8050121.Search in Google Scholar PubMed PubMed Central

Kirkley, K.S., Popichak, K.A., Afzali, M.F., Legare, M.E., and Tjalkens, R.B. (2017). Microglia amplify inflammatory activation of astrocytes in manganese neurotoxicity. J. Neuroinflammation 14: 99, https://doi.org/10.1186/s12974-017-0871-0.Search in Google Scholar PubMed PubMed Central

Klegeris, A., Walker, D.G., and McGeer, P.L. (1997). Regulation of glutamate in cultures of human monocytic THP-1 and astrocytoma U-373 MG cells. J. Neuroimmunol. 78: 152–161, https://doi.org/10.1016/s0165-5728(97)00094-5.Search in Google Scholar PubMed

Klein, R.S., Williams, K.C., Alvarez-Hernandez, X., Westmoreland, S., Force, T., Lackner, A.A., and Luster, A.D. (1999). Chemokine receptor expression and signaling in macaque and human fetal neurons and astrocytes: implications for the neuropathogenesis of AIDS. J. Immunol. 163: 1636–1646, https://doi.org/10.4049/jimmunol.163.3.1636.Search in Google Scholar

Kremlev, S.G., Gaurnier-Hausser, A.L., Del Valle, L., Perez-Liz, G., Dimitrov, S., and Tuszynski, G. (2008). Angiocidin promotes pro-inflammatory cytokine production and antigen presentation in multiple sclerosis. J. Neuroimmunol. 194: 132–142, https://doi.org/10.1016/j.jneuroim.2007.11.003.Search in Google Scholar PubMed

Kulesza, A., Paczek, L., and Burdzinska, A. (2023). The role of COX-2 and PGE2 in the regulation of immunomodulation and other functions of mesenchymal stromal cells. Biomedicines 11: 445, https://doi.org/10.3390/biomedicines11020445.Search in Google Scholar PubMed PubMed Central

Kulkarni, A., Ganesan, P., and O’Donnell, L.A. (2016). Interferon gamma: influence on neural stem cell function in neurodegenerative and neuroinflammatory disease. Clin. Med. Insights Pathol. 9: 9–19, https://doi.org/10.4137/CPath.S40497.Search in Google Scholar PubMed PubMed Central

Kuno, R., Wang, J., Kawanokuchi, J., Takeuchi, H., Mizuno, T., and Suzumura, A. (2005). Autocrine activation of microglia by tumor necrosis factor-α. J. Neuroimmunol. 162: 89–96, https://doi.org/10.1016/j.jneuroim.2005.01.015.Search in Google Scholar PubMed

Kwon, H.S. and Koh, S. (2020). Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes. Transl. Neurodegener. 9: 42, https://doi.org/10.1186/s40035-020-00221-2.Search in Google Scholar PubMed PubMed Central

Lanfranco, M.F., Mocchetti, I., Burns, M.P., and Villapol, S. (2018). Glial- and neuronal-specific expression of CCL5 mRNA in the rat brain. Front. Neuroanat. 11: 137, https://doi.org/10.3389/fnana.2017.00137.Search in Google Scholar PubMed PubMed Central

Lanjakornsiripan, D., Pior, B.J., Kawaguchi, D., Furutachi, S., Tahara, T., Katsuyama, Y., Suzuki, Y., Fukazawa, Y., and Gotoh, Y. (2018). Layer-specific morphological and molecular differences in neocortical astrocytes and their dependence on neuronal layers. Nat. Commun. 9: 1623, https://doi.org/10.1038/s41467-018-03940-3.Search in Google Scholar PubMed PubMed Central

Lawrence, J.M., Schardien, K., Wigdahl, B., and Nonnemacher, M.R. (2023). Roles of neuropathology-associated reactive astrocytes: a systematic review. Acta Neuropathol. Commun. 11: 42, https://doi.org/10.1186/s40478-023-01526-9.Search in Google Scholar PubMed PubMed Central

Lee, R.K.K., Knapp, S., and Wurtman, R.J. (1999). Prostaglandin E2 stimulates amyloid precursor protein gene expression: inhibition by immunosuppressants. J. Neurosci. 19: 940–947, https://doi.org/10.1523/jneurosci.19-03-00940.1999.Search in Google Scholar

Lee, S.Y. and Chung, W. (2021). The roles of astrocytic phagocytosis in maintaining homeostasis of brains. J. Pharmacol. Sci. 145: 223–227, https://doi.org/10.1016/j.jphs.2020.12.007.Search in Google Scholar PubMed

Levy, N., Milikovsky, D.Z., Baranauskas, G., Vinogradov, E., David, Y., Ketzef, M., Abutbul, S., Weissberg, I., Kamintsky, L., Fleidervish, I.A., et al.. (2015). Differential TGF-Β signaling in glial subsets underlies IL-6–mediated epileptogenesis in mice. J. Immunol. 195: 1713–1722, https://doi.org/10.4049/jimmunol.1401446.Search in Google Scholar PubMed

Li, J., Shui, X., Sun, R., Wan, L., Zhang, B., Xiao, B., and Luo, Z. (2021). Microglial phenotypic transition: signaling pathways and influencing modulators involved in regulation in central nervous system diseases. Front. Cell. Neurosci. 15: 736310, https://doi.org/10.3389/fncel.2021.736310.Search in Google Scholar PubMed PubMed Central

Li, K., Li, J., Zheng, J., and Qin, S. (2019). Reactive astrocytes in neurodegenerative diseases. Aging Dis. 10: 664–675, https://doi.org/10.14336/ad.2018.0720.Search in Google Scholar PubMed PubMed Central

Li, N., Sul, J.Y., and Haydon, P.G. (2003). A calcium-induced calcium influx factor, nitric oxide, modulates the refilling of calcium stores in astrocytes. J. Neurosci. 23: 10302–10310, https://doi.org/10.1523/jneurosci.23-32-10302.2003.Search in Google Scholar

Li, S., Gu, X., and Yi, S. (2017). The regulatory effects of transforming growth factor-Β on nerve regeneration. Cell Transplant. 26: 381–394, https://doi.org/10.3727/096368916x693824.Search in Google Scholar PubMed PubMed Central

Liddelow, S.A., Guttenplan, K.A., Clarke, L.E., Bennett, F.C., Bohlen, C.J., Schirmer, L., Bennett, M.L., Münch, A.E., Chung, W., Peterson, T.C., et al.. (2017). Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541: 481–487, https://doi.org/10.1038/nature21029.Search in Google Scholar PubMed PubMed Central

Lindholm, D., Ċastrén, E., Kiefer, R., Zafra, F., and Thoenen, H. (1992). Transforming growth factor-beta 1 in the rat brain: increase after injury and inhibition of astrocyte proliferation. J. Cell Biol. 117: 395–400, https://doi.org/10.1083/jcb.117.2.395.Search in Google Scholar PubMed PubMed Central

Lindhout, I.A., Murray, T.E., Richards, C.M., and Klegeris, A. (2021). Potential neurotoxic activity of diverse molecules released by microglia. Neurochem. Int. 148: 105117, https://doi.org/10.1016/j.neuint.2021.105117.Search in Google Scholar PubMed

Liu, C., Cui, G., Zhu, M., Kang, X., and Guo, H. (2014a). Neuroinflammation in Alzheimer’s disease: chemokines produced by astrocytes and chemokine receptors. Int. J. Clin. Exp. Pathol. 7: 8342–8355.Search in Google Scholar

Liu, X., Shah, A., Gangwani, M.R., Silverstein, P.S., Fu, M., and Kumar, A. (2014b). HIV-1 Nef induces CCL5 production in astrocytes through p38-MAPK and PI3K/AKT pathway and utilizes NF-KB, CEBP and AP-1 transcription factors. Sci. Rep. 4: 4450, https://doi.org/10.1038/srep04450.Search in Google Scholar PubMed PubMed Central

Liu, G.J., Kalous, A., Werry, E.L., and Bennett, M.R. (2006). Purine release from spinal cord microglia after elevation of calcium by glutamate. Mol. Pharmacol. 70: 851–859, https://doi.org/10.1124/mol.105.021436.Search in Google Scholar PubMed

Liu, J., Cao, S., Kim, S., Chung, E.Y., Homma, Y., Guan, X., Jimenez, V., and Ma, X. (2005). Interleukin-12: an update on its immunological activities, signaling and regulation of gene expression. Curr. Immunol. Rev. 1: 119–137, https://doi.org/10.2174/1573395054065115.Search in Google Scholar PubMed PubMed Central

Luchena, C., Zuazo-Ibarra, J., Valero, J., Matute, C., Alberdi, E., and Capetillo‐Zarate, E. (2022). A neuron, microglia, and astrocyte triple co-culture model to study Alzheimer’s disease. Front. Aging Neurosci. 14: 844534, https://doi.org/10.3389/fnagi.2022.844534.Search in Google Scholar PubMed PubMed Central

Luo, J. (2022). TGF-β as a key modulator of astrocyte reactivity: disease relevance and therapeutic implications. Biomedicines 10: 1206, https://doi.org/10.3390/biomedicines10051206.Search in Google Scholar PubMed PubMed Central

Luo, Y., Berman, M.A., Zhai, Q., Fischer, F.R., Abromson-Leeman, S.R., Zhang, Y., Kuziel, W.A., Gerard, C., and Dorf, M.E. (2002). RANTES stimulates inflammatory cascades and receptor modulation in murine astrocytes. Glia 39: 19–30, https://doi.org/10.1002/glia.10079.Search in Google Scholar PubMed

Madeira, C., Vargas-Lopes, C., Brandão, C.O., Reis, T., Laks, J., Panizzutti, R., and Ferreira, S.T. (2018). Elevated glutamate and glutamine levels in the cerebrospinal fluid of patients with probable Alzheimer’s disease and depression. Front. Psychiatry 9: 561, https://doi.org/10.3389/fpsyt.2018.00561.Search in Google Scholar PubMed PubMed Central

Mahmoud, S., Gharagozloo, M., Simard, C., and Gris, D. (2019). Astrocytes maintain glutamate homeostasis in the CNS by controlling the balance between glutamate uptake and release. Cells 8: 184, https://doi.org/10.3390/cells8020184.Search in Google Scholar PubMed PubMed Central

Mäkelä, J., Koivuniemi, R., Korhonen, L., and Lindholm, D. (2010). Interferon-γ produced by microglia and the neuropeptide PACAP have opposite effects on the viability of neural progenitor cells. PLoS One 5: e11091, https://doi.org/10.1371/journal.pone.0011091.Search in Google Scholar PubMed PubMed Central

Mastenbroek, L.J.M., Kooistra, S.M., Eggen, B.J.L., and Prins, J.R. (2024). The role of microglia in early neurodevelopment and the effects of maternal immune activation. Semin. Immunopathol. 46: 1, https://doi.org/10.1007/s00281-024-01017-6.Search in Google Scholar PubMed PubMed Central

Matejuk, A. and Ransohoff, R.M. (2020). Crosstalk between astrocytes and microglia: an overview. Front. Immunol. 11: 1416, https://doi.org/10.3389/fimmu.2020.01416.Search in Google Scholar PubMed PubMed Central

McKenna, M.C. (2007). The glutamate-glutamine cycle is not stoichiometric: fates of glutamate in brain. J. Neurosci. Res. 85: 3347–3358, https://doi.org/10.1002/jnr.21444.Search in Google Scholar PubMed

McTigue, D.M., Popovich, P.G., Morgan, T.E., and Stokes, B.T. (2000). Localization of transforming growth factor-β1 and receptor mRNA after experimental spinal cord injury. Exp. Neurol. 163: 220–230, https://doi.org/10.1006/exnr.2000.7372.Search in Google Scholar PubMed

Michaelson, M.D., Mehler, M.F., Xu, H., Gross, R.E., and Kessler, J.A. (1996). Interleukin-7 is trophic for embryonic neurons and is expressed in developing brain. Dev. Biol. 179: 251–263, https://doi.org/10.1006/dbio.1996.0255.Search in Google Scholar PubMed

Miller, K.E., Hoffman, E.M., Sutharshan, M., and Schechter, R. (2011). Glutamate pharmacology and metabolism in peripheral primary afferents: physiological and pathophysiological mechanisms. Pharmacol. Ther. 130: 283–309, https://doi.org/10.1016/j.pharmthera.2011.01.005.Search in Google Scholar PubMed PubMed Central

Miller, M.W. and Luo, J. (2000). Effects of ethanol and basic fibroblast growth factor on the transforming growth factor beta1 regulated proliferation of cortical astrocytes and C6 astrocytoma cells. Alcohol Clin. Exp. Res. 26: 671–676, https://doi.org/10.1097/00000374-200205000-00011.Search in Google Scholar

Minkiewicz, J., Vaccari, R., and Keane, R.W. (2013). Human astrocytes express a novel NLRP2 inflammasome. Glia 61: 1113–1121, https://doi.org/10.1002/glia.22499.Search in Google Scholar PubMed

Miyoshi, K., Obata, K., Kondo, T., Okamura, H., and Noguchi, K. (2008). Interleukin-18-mediated microglia/astrocyte interaction in the spinal cord enhances neuropathic pain processing after nerve injury. J. Neurosci. 28: 12775–12787, https://doi.org/10.1523/jneurosci.3512-08.2008.Search in Google Scholar PubMed PubMed Central

Mizuno, T., Sawada, M., Marunouchi, T., and Suzumura, A. (1994). Production of interleukin-10 by mouse glial cells in culture. Biochem. Biophys. Res. Commun. 205: 1907–1915, https://doi.org/10.1006/bbrc.1994.2893.Search in Google Scholar PubMed

Mölders, A., Koch, A., Menke, R., and Klöcker, N. (2018). Heterogeneity of the astrocytic AMPA-receptor transcriptome. Glia 66: 2604–2616, https://doi.org/10.1002/glia.23514.Search in Google Scholar PubMed

Montine, T.J., Sidell, K.R., Crews, B.C., Markesbery, W.R., Marnett, L.J., Roberts, L.J., and Morrow, J.D. (1999). Elevated CSF prostaglandin E2 levels in patients with probable AD. Neurology 53: 1495–1498, https://doi.org/10.1212/wnl.53.7.1495.Search in Google Scholar PubMed

Morel, L., Chiang, M.S.R., Higashimori, H., Shoneye, T., Iyer, L.K., Yelick, J., Tai, A., and Yang, Y. (2017). Molecular and functional properties of regional astrocytes in the adult brain. J. Neurosci. 37: 8706–8717, https://doi.org/10.1523/jneurosci.3956-16.2017.Search in Google Scholar

Moussa, N. and Dayoub, N. (2023). Exploring the role of COX-2 in Alzheimer’s disease: potential therapeutic implications of COX-2 inhibitors. Saudi Pharm. J. 31: 101729, https://doi.org/10.1016/j.jsps.2023.101729.Search in Google Scholar PubMed PubMed Central

Muller, M.S. and Taylor, C.W. (2017). ATP evokes Ca2+ signals in cultured foetal human cortical astrocytes entirely through G protein-coupled P2Y receptors. J. Neurochem. 142: 876–885, https://doi.org/10.1111/jnc.14119.Search in Google Scholar PubMed PubMed Central

Murana, E., Pagani, F., Basilico, B., Sundukova, M., Batti, L., Di Angelantonio, S., Cortese, B., Grimaldi, A., Francioso, A., Heppenstall, P., et al.. (2017). ATP release during cell swelling activates a Ca2+-dependent Cl- current by autocrine mechanism in mouse hippocampal microglia. Sci. Rep. 7: 4184.10.1038/s41598-017-04452-8Search in Google Scholar PubMed PubMed Central

Murray, T.E., Richards, C.M., Robert-Gostlin, V.N., Bernath, A.K., Lindhout, I.A., and Klegeris, A. (2022). Potential neurotoxic activity of diverse molecules released by astrocytes. Brain Res. Bull. 189: 80–101, https://doi.org/10.1016/j.brainresbull.2022.08.015.Search in Google Scholar PubMed

Nagano, T., Tsuda, N., Fujimura, K., Ikezawa, Y., Higashi, Y., and Kimura, S.H. (2021). Prostaglandin E2 increases the expression of cyclooxygenase-2 in cultured rat microglia. J. Neuroimmunol. 361: 577724, https://doi.org/10.1016/j.jneuroim.2021.577724.Search in Google Scholar PubMed

Nash, B., Ioannidou, K., and Barnett, S.C. (2010). Astrocyte phenotypes and their relationship to myelination. J. Anat. 219: 44–52, https://doi.org/10.1111/j.1469-7580.2010.01330.x.Search in Google Scholar PubMed PubMed Central

Neniskyte, U. and Gross, C. (2017). Errant gardeners: glial-cell-dependent synaptic pruning and neurodevelopmental disorders. Nat. Rev. Neurosci. 18: 658–670, https://doi.org/10.1038/nrn.2017.110.Search in Google Scholar PubMed

Niswender, C.M. and Conn, P.J. (2010). Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu. Rev. Pharmacol. Toxicol. 50: 295–322, https://doi.org/10.1146/annurev.pharmtox.011008.145533.Search in Google Scholar PubMed PubMed Central

Noguchi, Y., Shinozaki, Y., Fujishita, K., Shibata, K., Imura, Y., Morizawa, Y., Gachet, C., and Koizumi, S. (2013). Astrocytes protect neurons against methylmercury via ATP/P2Y1 receptor-mediated pathways in astrocytes. PLoS One 8: e57898, https://doi.org/10.1371/journal.pone.0057898.Search in Google Scholar PubMed PubMed Central

Norden, D.M., Fenn, A.M., Dugan, A., and Godbout, J.P. (2014). TGFβ produced by IL-10 redirected astrocytes attenuates microglial activation. Glia 62: 881–895, https://doi.org/10.1002/glia.22647.Search in Google Scholar PubMed PubMed Central

Ojala, J., Alafuzoff, I., Herukka, S., Van Groen, T., Tanila, H., and Pirttilä, T. (2009). Expression of interleukin-18 is increased in the brains of Alzheimer’s disease patients. Neurobiol. Aging 30: 198–209, https://doi.org/10.1016/j.neurobiolaging.2007.06.006.Search in Google Scholar PubMed

Oppermann, M. (2004). Chemokine receptor CCR5: insights into structure, function, and regulation. Cell. Signal. 16: 1201–1210, https://doi.org/10.1016/j.cellsig.2004.04.007.Search in Google Scholar PubMed

Orlando, A., Manuel, V., Belem, T., Howe, A.G., Patricia, D., Miquelajáuregui Graf, A., María, A., and Estrada-Sánchez, A.M. (2023). Revealing the contribution of astrocytes to glutamatergic neuronal transmission. Front. Cell. Neurosci. 16: 1037641, https://doi.org/10.3389/fncel.2022.1037641.Search in Google Scholar PubMed PubMed Central

Panagiotakopoulou, V., Ivanyuk, D., De Cicco, S., Haq, W., Arsić, A., Yu, C., Messelodi, D., Oldrati, M., Schöndorf, D.C., Perez, M., et al.. (2020). Interferon-γ signaling synergizes with LRRK2 in neurons and microglia derived from human induced pluripotent stem cells. Nat. Commun. 11: 5163, https://doi.org/10.1038/s41467-020-18755-4.Search in Google Scholar PubMed PubMed Central

Paolicelli, R.C., Sierra, A., Stevens, B., Tremblay, M., Aguzzi, A., Ajami, B., Amit, I., Audinat, E., Bechmann, I., Bennett, M.L., et al.. (2022). Microglia states and nomenclature: a field at its crossroads. Neuron 110: 3458–3483, https://doi.org/10.1016/j.neuron.2022.10.020.Search in Google Scholar PubMed PubMed Central

Park, J.Y., Pillinger, M.H., and Abramson, S.B. (2006). Prostaglandin E2 synthesis and secretion: the role of PGE2 synthases. Clin. Immunol. 119: 229–240, https://doi.org/10.1016/j.clim.2006.01.016.Search in Google Scholar PubMed

Park, K.W., Lee, H.G., Jin, B.K., and Lee, Y.B. (2007). Interleukin-10 endogenously expressed in microglia prevents lipopolysaccharide-induced neurodegeneration in the rat cerebral cortex in vivo. Exp. Mol. Med. 39: 812–819, https://doi.org/10.1038/emm.2007.88.Search in Google Scholar PubMed

Pascual, O., Ben Achour, S., Rostaing, P., Triller, A., and Bessis, A. (2012). Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission. Proc. Natl. Acad. Sci. U. S. A. 109: E197–E205, https://doi.org/10.1073/pnas.1111098109.Search in Google Scholar PubMed PubMed Central

Pellerin, L. and Magistretti, P.J. (1994). Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc. Natl. Acad. Sci. U. S. A. 91: 10625–10629, https://doi.org/10.1073/pnas.91.22.10625.Search in Google Scholar PubMed PubMed Central

Perlmutter, L.S., Scott, S.A., Barrón, E., and Chui, H.C. (1992). MHC class II-positive microglia in human brain: association with Alzheimer lesions. J. Neurosci. Res. 33: 549–558, https://doi.org/10.1002/jnr.490330407.Search in Google Scholar PubMed

Pittaluga, A. (2017). CCL5–glutamate cross-talk in astrocyte-neuron communication in multiple sclerosis. Front. Immunol. 8: 1079, https://doi.org/10.3389/fimmu.2017.01079.Search in Google Scholar PubMed PubMed Central

Planas-Fontánez, T.M., Dreyfus, C.F., and Saitta, K.S. (2020). Reactive astrocytes as therapeutic targets for brain degenerative diseases: roles played by metabotropic glutamate receptors. Neurochem. Res. 45: 541–550, https://doi.org/10.1007/s11064-020-02968-6.Search in Google Scholar PubMed PubMed Central

Porro, C., Cianciulli, A., and Panaro, M.A. (2020). The regulatory role of IL-10 in neurodegenerative diseases. Biomolecules 10: 1017, https://doi.org/10.3390/biom10071017.Search in Google Scholar PubMed PubMed Central

Prehn, J.H. and Miller, R.J. (1996). Opposite effects of TGF-β1 on rapidly- and slowly-triggered excitotoxic injury. Neuropharmacology 35: 249–256, https://doi.org/10.1016/0028-3908(96)00001-9.Search in Google Scholar PubMed

Rampe, D., Wang, L., and Ringheim, G.E. (2004). P2X7 receptor modulation of β-amyloid- and LPS-induced cytokine secretion from human macrophages and microglia. J. Neuroimmunol. 147: 56–61, https://doi.org/10.1016/j.jneuroim.2003.10.014.Search in Google Scholar PubMed

Rasley, A., Marriott, I., Halberstadt, C.R., Bost, K.L., and Anguita, J. (2004). Substance P augments Borrelia burgdorferi-induced prostaglandin E2 production by murine microglia. J. Immunol. 172: 5707–5713, https://doi.org/10.4049/jimmunol.172.9.5707.Search in Google Scholar PubMed

Rasley, A., Tranguch, S.L., Rati, D.M., and Marriott, I. (2006). Murine glia express the immunosuppressive cytokine, interleukin-10, following exposure to Borrelia burgdorferi or Neisseria meningitidis. Glia 53: 583–592, https://doi.org/10.1002/glia.20314.Search in Google Scholar PubMed

Rezaie, P., Trillo‐Pazos, G., Everall, I.P., and Male, D.K. (2001). Expression of β‐chemokines and chemokine receptors in human fetal astrocyte and microglial co‐cultures: potential role of chemokines in the developing CNS. Glia 37: 64–75, https://doi.org/10.1002/glia.1128.Search in Google Scholar PubMed

Ricciotti, E. and FitzGerald, G.A. (2011). Prostaglandins and inflammation. Arterioscler. Thromb. Vasc. Biol. 31: 986–1000, https://doi.org/10.1161/atvbaha.110.207449.Search in Google Scholar

Rich, J., Zhang, M., Datto, M.B., Bigner, D.D., and Wang, X.F. (1999). Transforming growth factor-Β-mediated p15(INK4B) induction and growth inhibition in astrocytes is SMAD3-dependent and a pathway prominently altered in human glioma cell lines. J. Biol. Chem. 274: 35053–35058, https://doi.org/10.1074/jbc.274.49.35053.Search in Google Scholar PubMed

Rivera, A., Vanzulli, I., and Butt, A.M. (2016). A central role for ATP signalling in glial interactions in the CNS. Curr. Drug Targets 17: 1829–1833, https://doi.org/10.2174/1389450117666160711154529.Search in Google Scholar PubMed

Rodrigues, R.J., Tomé, A.R., and Cunha, R.A. (2015). ATP as a multi-target danger signal in the brain. Front. Neurosci. 9: 148, https://doi.org/10.3389/fnins.2015.00148.Search in Google Scholar PubMed PubMed Central

Rose, C.R., Felix, L., Zeug, A., Dietrich, D., Reiner, A., and Henneberger, C. (2017). Astroglial glutamate signaling and uptake in the hippocampus. Front. Mol. Neurosci. 10: 451, https://doi.org/10.3389/fnmol.2017.00451.Search in Google Scholar PubMed PubMed Central

Rostène, W., Kitabgi, P., and Parsadaniantz, S.M. (2007). Chemokines: a new class of neuromodulator? Nat. Rev. Neurosci. 8: 895–903, https://doi.org/10.1038/nrn2255.Search in Google Scholar PubMed

Rottman, J.B., Ganley, K.P., Williams, K., Wu, L., Mackay, C.R., and Ringler, D.J. (1997). Cellular localization of the chemokine receptor CCR5: correlation to cellular targets of HIV-1 infection. Am. J. Pathol. 151: 1341–1351.Search in Google Scholar

Roy, A., Mondal, S., Kordower, J.H., and Pahan, K. (2015). Attenuation of microglial CCL5 by NEMO-binding domain peptide inhibits the infiltration of CD8+ T cells in the nigra of hemiparkinsonian monkey. Neuroscience 302: 36–46, https://doi.org/10.1016/j.neuroscience.2015.03.011.Search in Google Scholar PubMed PubMed Central

Schafer, D.P., Lehrman, E.K., Kautzman, A.G., Koyama, R., Mardinly, A.R., Yamasaki, R., Ransohoff, R.M., Greenberg, M.E., Barres, B.A., and Stevens, B. (2012). Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74: 691–705, https://doi.org/10.1016/j.neuron.2012.03.026.Search in Google Scholar PubMed PubMed Central

Schmidt, S.I., Bogetofte, H., Ritter, L., Agergaard, J.B., Hammerich, D., Kabiljagic, A.A., Włodarczyk, A., López, S.G., Sørensen, M.D., Jørgensen, M.L., et al.. (2021). Microglia-secreted factors enhance dopaminergic differentiation of tissue- and IPSC-derived human neural stem cells. Stem Cell Rep. 16: 281–294, https://doi.org/10.1016/j.stemcr.2020.12.011.Search in Google Scholar PubMed PubMed Central

Shanaki-Bavarsad, M., Almolda, B., González, B., and Castellano, B. (2022). Astrocyte-targeted overproduction of IL-10 reduces neurodegeneration after TBI. Exp. Neurobiol. 31: 173–195, https://doi.org/10.5607/en21035.Search in Google Scholar PubMed PubMed Central

Sheng, W.S., Hu, S., Kravitz, F.H., Peterson, P.K., and Chao, C.C. (1995). Tumor necrosis factor alpha upregulates human microglial cell production of interleukin-10 in vitro. Clin. Diagn. Lab. Immunol. 2: 604–608, https://doi.org/10.1128/cdli.2.5.604-608.1995.Search in Google Scholar PubMed PubMed Central

Shi, S., Liang, D., Chen, Y., Xie, Y., Wang, Y., Wang, L., Wang, Z., and Qiao, Z. (2016). Gx-50 reduces β-amyloid-induced TNF-α, IL-1β, NO, and PGE2 expression and inhibits NF-κB signaling in a mouse model of Alzheimer’s disease. Eur. J. Immunol. 46: 665–676, https://doi.org/10.1002/eji.201545855.Search in Google Scholar PubMed

Shinozaki, Y., Nomura, M., Iwatsuki, K., Moriyama, Y., Gachet, C., and Koizumi, S. (2013). Microglia trigger astrocyte-mediated neuroprotection via purinergic gliotransmission. Sci. Rep. 4: 4329, https://doi.org/10.1038/srep04329.Search in Google Scholar PubMed PubMed Central

Šimončičová, E., Gonçalves de Andrade, E., Vecchiarelli, H.A., Awogbindin, I.O., Delage, C., and Tremblay, M. (2022). Present and future of microglial pharmacology. Trends Pharmacol. Sci. 43: 669–685, https://doi.org/10.1016/j.tips.2021.11.006.Search in Google Scholar PubMed

Skowronska, K., Obara-Michlewska, M., Zielinska, M., and Albrecht, J. (2019). NMDA receptors in astrocytes: in search for roles in neurotransmission and astrocytic homeostasis. Int. J. Mol. Sci. 20: 309.10.3390/ijms20020309Search in Google Scholar PubMed PubMed Central

Smith, B.C., Sinyuk, M., Jenkins, J.E., Psenicka, M.W., and Williams, J.L. (2020). The impact of regional astrocyte interferon-γ signaling during chronic autoimmunity: a novel role for the immunoproteasome. J. Neuroinflammation 17: 184, https://doi.org/10.1186/s12974-020-01861-x.Search in Google Scholar PubMed PubMed Central

Smith, J.A., Das, A., Ray, S.K., and Banik, N.L. (2012). Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. Brain Res. Bull. 87: 10–20, https://doi.org/10.1016/j.brainresbull.2011.10.004.Search in Google Scholar PubMed PubMed Central

Sørensen, C.E. and Novak, I. (2001). Visualization of ATP release in pancreatic acini in response to cholinergic stimulus: use of fluorescent probes and confocal microscopy. J. Biol. Chem. 276: 32925–32932, https://doi.org/10.1074/jbc.m103313200.Search in Google Scholar

Spielman, L.J., Bahniwal, M., Little, J.P., Walker, D.G., and Klegeris, A. (2015). Insulin modulates in vitro secretion of cytokines and cytotoxins by human glial cells. Curr. Alzheimer Res. 12: 684–693, https://doi.org/10.2174/1567205012666150710104428.Search in Google Scholar PubMed

Stanbrough, M., Rowen, D.W., and Magasanik, B. (1995). Role of the GATA factors Gln3p and Nil1p of Saccharomyces cerevisiae in the expression of nitrogen-regulated genes. Proc. Natl. Acad. Sci. U. S. A. 92: 9450–9454, https://doi.org/10.1073/pnas.92.21.9450.Search in Google Scholar PubMed PubMed Central

Stock, J.L., Shinjo, K., Burkhardt, J., Roach, M., Taniguchi, K., Ishikawa, T., Kim, S., Flannery, P.J., Coffman, T.M., McNeish, J.D., et al.. (2001). The prostaglandin E2 EP1 receptor mediates pain perception and regulates blood pressure. J. Clin. Invest. 107: 325–331, https://doi.org/10.1172/jci6749.Search in Google Scholar

Strle, K., Zhou, J.H., Shen, W.H., Broussard, S.R., Johnson, R.W., Freund, G.G., Dantzer, R., and Kelley, K.W. (2001). Interleukin-10 in the brain. Crit. Rev. Immunol. 21: 427–449.10.1615/CritRevImmunol.v21.i5.20Search in Google Scholar

Sugimoto, Y., Inazumi, T., and Tsuchiya, S. (2015). Roles of prostaglandin receptors in female reproduction. J. Biochem. 157: 73–80, https://doi.org/10.1093/jb/mvu081.Search in Google Scholar PubMed

Suk, K., Kim, S.Y., and Kim, H. (2001). Regulation of IL-18 production by IFNγ and PGE2 in mouse microglial cells: involvement of NF-kB pathway in the regulatory processes. Immunol. Lett. 77: 79–85, https://doi.org/10.1016/s0165-2478(01)00209-7.Search in Google Scholar PubMed

Sun, M., You, H., Hu, X., Luo, Y., Zhang, Z., Song, Y., An, J., and Lu, H. (2023). Microglia-astrocyte interaction in neural development and neural pathogenesis. Cells 12: 1942, https://doi.org/10.3390/cells12151942.Search in Google Scholar PubMed PubMed Central

Suzumura, A., Sawada, M., and Takayanagi, T. (1998). Production of interleukin-12 and expression of its receptors by murine microglia. Brain Res. 787: 139–142, https://doi.org/10.1016/s0006-8993(97)01166-9.Search in Google Scholar PubMed

Sznejder-Pachołek, A., Joniec-Maciejak, I., Wawer, A., Ciesielska, A., and Mirowska‐Guzel, D. (2017). The effect of α-synuclein on gliosis and IL-1α, TNFα, IFNγ, TGFβ expression in murine brain. Pharmacol. Rep. 69: 242–251, https://doi.org/10.1016/j.pharep.2016.11.003.Search in Google Scholar PubMed

Ta, T., Dikmen, H., Schilling, S., Chausse, B., Lewen, A., Hollnagel, J., and Kann, O. (2019). Priming of microglia with IFN-γ slows neuronal gamma oscillations in situ. Proc. Natl. Acad. Sci. U. S. A. 116: 4637–4642, https://doi.org/10.1073/pnas.1813562116.Search in Google Scholar PubMed PubMed Central

Takaki, J., Fujimori, K., Miura, M., Suzuki, T., Sekino, Y., and Sato, K. (2012). L-glutamate released from activated microglia downregulates astrocytic L-glutamate transporter expression in neuroinflammation: the “collusion” hypothesis for increased extracellular L-glutamate concentration in neuroinflammation. J. Neuroinflammation 9: 275, https://doi.org/10.1186/1742-2094-9-275.Search in Google Scholar PubMed PubMed Central

Takeuchi, H., Jin, S., Wang, J., Zhang, G., Kawanokuchi, J., Kuno, R., Sonobe, Y., Mizuno, T., and Suzumura, A. (2006). Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner. J. Biol. Chem. 281: 21362–21368, https://doi.org/10.1074/jbc.m600504200.Search in Google Scholar PubMed

Takeuchi, H. and Suzumura, A. (2014). Gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases. Front. Cell. Neurosci. 8: 189, https://doi.org/10.3389/fncel.2014.00189.Search in Google Scholar PubMed PubMed Central

Tan, J.J., Boudreault, F., Adam, D., Brochiero, E., and Grygorczyk, R. (2019). Type 2 secretory cells are primary source of ATP release in mechanically stretched lung alveolar cells. Am. J. Physiol. Lung Cell Mol. Physiol. 318: L49–L58, https://doi.org/10.1152/ajplung.00321.2019.Search in Google Scholar PubMed

Taoufik, Y., de Goër de Herve, M.G., Giron-Michel, J., Durali, D., Cazes, E., Tardieu, M., Azzarone, B., and Delfraissy, J.F. (2001). Human microglial cells express a functional IL-12 receptor and produce IL-12 following IL-12 stimulation. Eur. J. Immunol. 31: 3228–3239, https://doi.org/10.1002/1521-4141(200111)31:11<3228::aid-immu3228>3.0.co;2-7.10.1002/1521-4141(200111)31:11<3228::AID-IMMU3228>3.0.CO;2-7Search in Google Scholar

Tau, G. and Rothman, P. (1999). Biologic functions of the IFN-gamma receptors. Allergy 54: 1233–1251, https://doi.org/10.1034/j.1398-9995.1999.00099.x.Search in Google Scholar

Tichauer, J.E., Arellano, G., Acuña, E.F., González, L., Kannaiyan, N., Murgas, P., Panadero-Medianero, C., Ibañez-Vega, J., Burgos, P.I., Loda, E., et al.. (2023). Interferon-gamma ameliorates experimental autoimmune encephalomyelitis by inducing homeostatic adaptation of microglia. Front. Immunol. 14: 1191838, https://doi.org/10.3389/fimmu.2023.1191838.Search in Google Scholar

Tripathy, D., Thirumangalakudi, L., and Grammas, P. (2010). CCL5 upregulation in the Alzheimer’s disease brain: a possible neuroprotective role. Neurobiol. Aging 31: 8–16, https://doi.org/10.1016/j.neurobiolaging.2008.03.009.Search in Google Scholar

Tse, K.H., Chow, K.B.S., and Wise, H. (2016). PGE2 released by primary sensory neurons modulates toll-like receptor 4 activities through an EP4 receptor-dependent process. J. Neuroimmunol. 293: 8–16, https://doi.org/10.1016/j.jneuroim.2016.02.005.Search in Google Scholar PubMed

Tsilioni, I. and Theoharides, T.C. (2023). Recombinant SARS-COV-2 spike protein and its receptor binding domain stimulate release of different pro-inflammatory mediators via activation of distinct receptors on human microglia cells. Mol. Neurobiol. 60: 6704–6714, https://doi.org/10.1007/s12035-023-03493-7.Search in Google Scholar PubMed

Valerio, A., Ferrario, M., Martinez, F.O., Locati, M., Ghisi, V., Bresciani, L.G., Mantovani, A., and Spano, P. (2004). Gene expression profile activated by the chemokine CCL5/RANTES in human neuronal cells. J. Neurosci. Res. 78: 371–382, https://doi.org/10.1002/jnr.20250.Search in Google Scholar PubMed

Vandenberg, R.J. and Ryan, R.M. (2013). Mechanisms of glutamate transport. Physiol. Rev. 93: 1621–1657, https://doi.org/10.1152/physrev.00007.2013.Search in Google Scholar PubMed

Vargas, J.R., Takahashi, D.K., Thomson, K.E., and Wilcox, K.S. (2013). The expression of kainate receptor subunits in hippocampal astrocytes following experimentally induced status epilepticus. J. Neuropathol. Exp. Neurol. 72: 919–932, https://doi.org/10.1097/nen.0b013e3182a4b266.Search in Google Scholar

Verderio, C. and Matteoli, M. (2001). ATP mediates calcium signaling between astrocytes and microglial cells: modulation by IFN-γ. J. Immunol. 166: 6383–6391, https://doi.org/10.4049/jimmunol.166.10.6383.Search in Google Scholar PubMed

Vignali, D.A. and Kuchroo, V.K. (2012). IL-12 family cytokines: immunological playmakers. Nat. Immunol. 13: 722–728, https://doi.org/10.1038/ni.2366.Search in Google Scholar PubMed PubMed Central

von Kügelgen, I. and Hoffmann, K. (2016). Pharmacology and structure of P2Y receptors. Neuropharmacology 104: 50–61, https://doi.org/10.1016/j.neuropharm.2015.10.030.Search in Google Scholar PubMed

Walter, M.R. (2014). The molecular basis of IL-10 function: from receptor structure to the onset of signaling. Curr. Top. Microbiol. Immunol. 380: 191–212, https://doi.org/10.1007/978-3-662-43492-5_9.Search in Google Scholar PubMed PubMed Central

Wang, J., Liu, M., Zhang, X., Yang, G., and Chen, L. (2018). Physiological and pathophysiological implications of PGE2 and the PGE2 synthases in the kidney. Prostag. Other Lipid Mediat. 134: 1–6, https://doi.org/10.1016/j.prostaglandins.2017.10.006.Search in Google Scholar PubMed

Wang, T., Qin, L., Liu, B., Liu, Y., Wilson, B., Eling, T.E., Langenbach, R., Taniura, S., and Hong, J.-S. (2004). Role of reactive oxygen species in LPS-induced production of prostaglandin E2 in microglia. J. Neurochem. 88: 939–947, https://doi.org/10.1046/j.1471-4159.2003.02242.x.Search in Google Scholar PubMed

Wang, W.Y., Tan, M.S., Yu, J.T., and Tan, L. (2015). Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Ann. Transl. Med. 3: 136, https://doi.org/10.3978/j.issn.2305-5839.2015.03.49.Search in Google Scholar PubMed PubMed Central

Wang, X. and Suzuki, Y. (2007). Microglia produce IFN-γ independently from T cells during acute toxoplasmosis in the brain. J. Interferon Cytokine Res. 27: 599–605, https://doi.org/10.1089/jir.2006.0157.Search in Google Scholar PubMed

Wei, Y. and Li, X. (2022). Different phenotypes of microglia in animal models of Alzheimer disease. Immun. Ageing 19: 44, https://doi.org/10.1186/s12979-022-00300-0.Search in Google Scholar PubMed PubMed Central

Wendimu, M. and Hooks, S.B. (2022). Microglia phenotypes in aging and neurodegenerative diseases. Cells 11: 2091, https://doi.org/10.3390/cells11132091.Search in Google Scholar PubMed PubMed Central

Werry, E.L., Liu, G.J., Lovelace, M.D., Nagarajah, R., Hickie, I.B., and Bennett, M.R. (2011). Lipopolysaccharide-stimulated interleukin-10 release from neonatal spinal cord microglia is potentiated by glutamate. Neuroscience 175: 93–103, https://doi.org/10.1016/j.neuroscience.2010.10.080.Search in Google Scholar PubMed

Westmoreland, S.V., Halpern, E., and Lackner, A.A. (1998). Simian immunodeficiency virus encephalitis in rhesus macaques is associated with rapid disease progression. J. Neurovirol. 4: 260–268, https://doi.org/10.3109/13550289809114527.Search in Google Scholar PubMed

Williams, K., Dooley, N., Ulvestad, E., Becher, B., and Antel, J.P. (1996). IL-10 production by adult human derived microglial cells. Neurochem. Int. 29: 55–64, https://doi.org/10.1016/0197-0186(95)00138-7.Search in Google Scholar PubMed

Wilson, J.X., Peters, C.E., Sitar, S.M., Daoust, P., and Gelb, A.W. (2000). Glutamate stimulates ascorbate transport by astrocytes. Brain Res. 858: 61–66, https://doi.org/10.1016/s0006-8993(99)02433-6.Search in Google Scholar PubMed

Woo, J.J., Han, D., Wang, J.I., Park, J., Kim, H., and Kim, Y. (2017). Quantitative proteomics reveals temporal proteomic changes in signaling pathways during BV2 mouse microglial cell activation. J. Proteome Res. 16: 3419–3432, https://doi.org/10.1021/acs.jproteome.7b00445.Search in Google Scholar PubMed

Xie, L., Yin, Y., and Benowitz, L. (2021). Chemokine CCL5 promotes robust optic nerve regeneration and mediates many of the effects of CNTF gene therapy. Proc. Natl. Acad. Sci. U. S. A. 118: e2017282118, https://doi.org/10.1073/pnas.2017282118.Search in Google Scholar PubMed PubMed Central

Yamanishi, K., Doe, N., Mukai, K., Hashimoto, T., Gamachi, N., Hara, M., Watanabe, Y., Yamanishi, C., Yagi, H., Okamura, H., et al.. (2022). Acute stress induces severe neural inflammation and overactivation of glucocorticoid signaling in interleukin-18-deficient mice. Transl. Psychiatry 12: 404, https://doi.org/10.1038/s41398-022-02175-7.Search in Google Scholar PubMed PubMed Central

Yang, S., Simtchouk, S., Gibon, J., and Klegeris, A. (2023). Regulation of the phagocytic activity of astrocytes by neuroimmune mediators endogenous to the central nervous system. PLoS One 18: e0289169, https://doi.org/10.1371/journal.pone.0289169.Search in Google Scholar PubMed PubMed Central

Yoo, H.-J. and Kwon, M.-S. (2022). Aged microglia in neurodegenerative diseases: microglia lifespan and culture methods. Front. Aging Neurosci. 13: 766267, https://doi.org/10.3389/fnagi.2021.766267.Search in Google Scholar PubMed PubMed Central

Zhang, D., Hu, X., Qian, L., Wilson, B., Lee, C., Flood, P., Langenbach, R., and Hong, J. (2009). Prostaglandin E2 released from activated microglia enhances astrocyte proliferation in vitro. Toxicol. Appl. Pharmacol. 238: 64–70, https://doi.org/10.1016/j.taap.2009.04.015.Search in Google Scholar PubMed PubMed Central

Zhang, H.-Y., Wang, Y., He, Y., Wang, T., Huang, X.-H., Zhao, C.-M., Zhang, L., Li, S.-W., Wang, C., Qu, Y.-N., et al.. (2020). A1 astrocytes contribute to murine depression-like behavior and cognitive dysfunction, which can be alleviated by IL-10 or fluorocitrate treatment. J. Neuroinflammation 17: 200, https://doi.org/10.1186/s12974-020-01871-9.Search in Google Scholar PubMed PubMed Central

Zhang, Y., Sloan, S.A., Clarke, L.E., Caneda, C., Plaza, C.A., Blumenthal, P.D., Vogel, H., Steinberg, G.K., Edwards, M.S., Li, G., et al.. (2016). Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse. Neuron 89: 37–53, https://doi.org/10.1016/j.neuron.2015.11.013.Search in Google Scholar PubMed PubMed Central

Zhou, J., Geng, Y., Su, T., Wang, Q., Ren, Y., Zhao, J., Fu, C., Weber, M., Lin, H., Kaminker, J.S., et al.. (2022). NMDA receptor-dependent prostaglandin-endoperoxide synthase 2 induction in neurons promotes glial proliferation during brain development and injury. Cell Rep. 38: 110557, https://doi.org/10.1016/j.celrep.2022.110557.Search in Google Scholar PubMed

Zhou, X., Spittau, B., and Krieglstein, K. (2012). TGFβ signalling plays an important role in IL4-induced alternative activation of microglia. J. Neuroinflammation 9: 210, https://doi.org/10.1186/1742-2094-9-210.Search in Google Scholar PubMed PubMed Central

Zhou, Y. and Danbolt, N.C. (2014). Glutamate as a neurotransmitter in the healthy brain. J. Neural. Transm. 121: 799–817, https://doi.org/10.1007/s00702-014-1180-8.Search in Google Scholar PubMed PubMed Central

Zonta, M., Angulo, M.C., Gobbo, S., Rosengarten, B., Hossmann, K., Pozzan, T., and Carmignoto, G. (2003). Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nat. Neurosci. 6: 43–50, https://doi.org/10.1038/nn980.Search in Google Scholar PubMed

Received: 2024-06-10
Accepted: 2024-08-12
Published Online: 2024-09-03
Published in Print: 2025-01-29

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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