The effect of maternal diabetes on the expression of gamma-aminobutyric acid and metabotropic glutamate receptors in male newborn rats’ inferior colliculi
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Maryam Ghenaatgar-Kasbi
, Mohammad Rezaei
, Payam Moharreri
, Hamid Heidarian Miri
, Ghasem Sazegar
and Hossein Haghir
Abstract
Objectives
Few studies have examined the molecular alterations in the auditory pathway of infants of diabetic mothers, notwithstanding the fact that maternal diabetes may have an impact on the development of the neonatal peripheral and central nervous systems. Male newborn rats were studied to determine how maternal diabetes affected the expression of gamma-aminobutyric acid (GABAAα1 and GABAB1) and metabotropic glutamate (mGlu2) receptors in the inferior colliculus (IC) in this research.
Methods
Female rats were given a single intraperitoneal injection of streptozotocin (STZ) at a 65 mg/kg dose to develop a model of diabetic mothers. The study population was split into sham, diabetes without treatment, and diabetes with insulin groups. Their male neonatal rats were anesthetized on P0, P7, and P14 after mating and delivery. The receptors’ distribution pattern was studied using immunohistochemistry (IHC).
Results
Pairwise comparison in the groups revealed that the GABA receptors (Aα1 and B1) were significantly downregulated in the diabetes without treatment group (p<0.001). Furthermore, pairwise comparison in the groups indicated significant mGlu2 upregulation in the diabetes without treatment group (p<0.001). Regarding the concentration of all receptors, there was no discernible distinction between the diabetes with insulin and sham groups.
Conclusions
This investigation showed that the concentration of GABAAα1 and GABAB1 receptors decreased significantly over time, whereas the concentration of mGlu2 receptors increased significantly over time in male neonatal rats born to streptozotocin-induced diabetic mothers.
Funding source: Mashhad University of Medical Sciences
Award Identifier / Grant number: 981584
Acknowledgments
Authors are grateful to Dr. Somaye Fallahnezhad, Dr. Hamideh Babaloo, and Dr. Fatemeh Tahmasebi.
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Research funding: The study is the results of Maryam Ghenaatgar-Kasbi’s MSc thesis. Deputy Research of Mashhad University of Medical Sciences (MUMS) funded this study with a grant number of 981584.
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Author contribution: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Not applicable.
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Ethical approval: The Ethics Committee of the Mashhad University of Medical Sciences approved this research (IR.MUMS.MEDICAL.REC.1399.446).
References
1. Linder, K, Schleger, F, Kiefer-Schmidt, I, Fritsche, L, Kümmel, S, Heni, M, et al.. Gestational diabetes impairs human fetal postprandial brain activity. J Clin Endocrinol Metab 2015;100:4029–36. https://doi.org/10.1210/jc.2015-2692.Search in Google Scholar PubMed
2. Federation, ID. IDF diabetes atlas, 8th ed. Brussels: International diabetes federation; 2017:905–11 pp.Search in Google Scholar
3. Zhou, B, Lu, Y, Hajifathalian, K, Bentham, J, Di Cesare, M, Danaei, G, et al.. Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet 2016;387:1513–30. https://doi.org/10.1016/s0140-6736(16)00618-8.Search in Google Scholar PubMed PubMed Central
4. Stanton, SG, Ryerson, E, Moore, SL, Sullivan-Mahoney, M, Couch, SC. Hearing screening outcomes in infants of pregestational diabetic mothers. 2005.10.1044/1059-0889(2005/008)Search in Google Scholar PubMed
5. Furman, BL. Streptozotocin‐induced diabetic models in mice and rats. Curr Protoc Pharmacol 2015;70:1–20. https://doi.org/10.1002/0471141755.ph0547s70.Search in Google Scholar PubMed
6. Van Noort, J. The structure and connections of the inferior colliculus: an investigation of the lower auditory system. Assen: van Gorcum; 1969.Search in Google Scholar
7. Richardson, B, Sottile, S, Caspary, D. Mechanisms of GABAergic and cholinergic neurotransmission in auditory thalamus: impact of aging. Hear Res 2021;402:108003. https://doi.org/10.1016/j.heares.2020.108003.Search in Google Scholar PubMed PubMed Central
8. Gassmann, M, Bettler, B. Regulation of neuronal GABAB receptor functions by subunit composition. Nat Rev Neurosci 2012;13:380–94. https://doi.org/10.1038/nrn3249.Search in Google Scholar PubMed
9. Caspary, DM, Milbrandt, JC, Helfert, RH. Central auditory aging: GABA changes in the inferior colliculus. Exp Gerontol 1995;30:349–60. https://doi.org/10.1016/0531-5565(94)00052-5.Search in Google Scholar PubMed
10. Hu, N-W, Ondrejcak, T, Rowan, MJ. Glutamate receptors in preclinical research on Alzheimer’s disease: update on recent advances. Pharmacol Biochem Behav 2012;100:855–62. https://doi.org/10.1016/j.pbb.2011.04.013.Search in Google Scholar PubMed
11. Mehta, A, Prabhakar, M, Kumar, P, Deshmukh, R, Sharma, P. Excitotoxicity: bridge to various triggers in neurodegenerative disorders. Eur J Pharmacol 2013;698:6–18. https://doi.org/10.1016/j.ejphar.2012.10.032.Search in Google Scholar PubMed
12. Institute of Laboratory Animal Resources (US), Committee on Care, Use of Laboratory Animals. Guide for the care and use of laboratory animals. US Department of Health and Human Services, Public Health Service, National Institutes of Health; 1986:83 p. No. 86–23.Search in Google Scholar
13. Wu, K, Huan, Y. Streptozotocin-induced diabetic models in mice and rats. Curr Protoc Pharmacol 2008;40:1–14. https://doi.org/10.1002/0471141755.ph0547s40.Search in Google Scholar PubMed
14. Yousefzadeh, N, Jeddi, S, Ghasemi, A. Induction of euthanasia using carbon dioxide in rat: an overview of the available practical guidelines. EBNESINA 2021;23:81–91.Search in Google Scholar
15. Ghenaatgar-Kasbi, M, Sazegar, G, Fallahnezhad, S, Babaloo, H, Tahmasebi, F, Haghir, H. The distribution pattern of M2 and Adrenergicα2 receptors on inferior colliculi in male newborns of diabetic rats. Neurosci Lett 2022;787:136820. https://doi.org/10.1016/j.neulet.2022.136820.Search in Google Scholar PubMed
16. Paxinos, G. The rat nervous system. Amsterdam: Academic Press; 2014.Search in Google Scholar
17. Ruifrok, AC, Johnston, DA. Quantification of histochemical staining by color deconvolution. Anal Quant Cytol Histol 2001;23:291–9.Search in Google Scholar
18. McIntyre, HD, Catalano, P, Zhang, C, Desoye, G, Mathiesen, ER, Damm, P. Gestational diabetes mellitus. Nat Rev Dis Prim 2019;5:1–19. https://doi.org/10.1038/s41572-019-0098-8.Search in Google Scholar PubMed
19. Elangovan, S, Spankovich, C, editors. Diabetes and auditory-vestibular pathology. Seminars in hearing. New York: Thieme Medical Publishers; 2019.10.1055/s-0039-1697033Search in Google Scholar PubMed PubMed Central
20. Antony, S, Peeyush Kumar, T, Kuruvilla, KP, George, N, Paulose, C. Decreased GABA receptor binding in the cerebral cortex of insulin induced hypoglycemic and streptozotocin induced diabetic rats. Neurochem Res 2010;35:1516–21. https://doi.org/10.1007/s11064-010-0210-7.Search in Google Scholar PubMed
21. Frisina, RD, Walton, JP. Age-related structural and functional changes in the cochlear nucleus. Hear Res 2006;216:216–23. https://doi.org/10.1016/j.heares.2006.02.003.Search in Google Scholar PubMed
22. Rance, G, Chisari, D, O’Hare, F, Roberts, L, Shaw, J, Jandeleit-Dahm, K, et al.. Auditory neuropathy in individuals with type 1 diabetes. J Neurol 2014;261:1531–6. https://doi.org/10.1007/s00415-014-7371-2.Search in Google Scholar PubMed
23. Makishima, K, Tanaka, K. Pathological changes of the inner ear and central auditory pathway in diabetics. Ann Otol Rhinol Laryngol 1971;80:218–28. https://doi.org/10.1177/000348947108000208.Search in Google Scholar PubMed
24. Faingold, CL. Role of GABA abnormalities in the inferior colliculus pathophysiology–audiogenic seizures. Hear Res 2002;168:223–37. https://doi.org/10.1016/s0378-5955(02)00373-8.Search in Google Scholar PubMed
25. Kuwada, S, Yin, T, Haberly, L, Wickesberg, R. Binaural interaction in the cat inferior colliculus: physiology and anatomy. In: Psychophysical, physiological, and behavioral studies in hearing. Delft: Delft University Press Delft; 1980:401–11 pp.10.1007/978-94-009-9144-6_56Search in Google Scholar
26. Farazifard, R, Wu, SH. Metabotropic glutamate receptors modulate glutamatergic and GABAergic synaptic transmission in the central nucleus of the inferior colliculus. Brain Res 2010;1325:28–40. https://doi.org/10.1016/j.brainres.2010.02.021.Search in Google Scholar PubMed
27. Marianowski, R, Liao, W-H, Van Den Abbeele, T, Fillit, P, Herman, P, Frachet, B, et al.. Expression of NMDA, AMPA and GABAA receptor subunit mRNAs in the rat auditory brainstem. I. Influence of early auditory deprivation. Hear Res 2000;150:1–11. https://doi.org/10.1016/s0378-5955(00)00166-0.Search in Google Scholar PubMed
28. Luján, R, Shigemoto, R, López-Bendito, G. Glutamate and GABA receptor signalling in the developing brain. Neuroscience 2005;130:567–80. https://doi.org/10.1016/j.neuroscience.2004.09.042.Search in Google Scholar PubMed
29. Fritschy, J, Paysan, J, Enna, A, Mohler, H. Switch in the expression of rat GABAA-receptor subtypes during postnatal development: an immunohistochemical study. J Neurosci 1994;14:5302–24. https://doi.org/10.1523/jneurosci.14-09-05302.1994.Search in Google Scholar
30. Hoyer, S. The brain insulin signal transduction system and sporadic (type II) Alzheimer disease: an update. J Neural Transm 2002;109:341–60. https://doi.org/10.1007/s007020200028.Search in Google Scholar PubMed
31. Li, P-A, Liu, G-J, He, QP, Floyd, RA, Siesjö, BK. Production of hydroxyl free radical by brain tissues in hyperglycemic rats subjected to transient forebrain ischemia. Free Radic Biol Med 1999;27:1033–40. https://doi.org/10.1016/s0891-5849(99)00152-5.Search in Google Scholar PubMed
32. Li, P-A, He, Q-P, Ouyang, Y-B, Liu, C-L, Hu, B-R, Siesjö, BK. Early release of cytochrome C and activation of caspase-3 in hyperglycemic rats subjected to transient forebrain ischemia. Brain Res 2001;896:69–76. https://doi.org/10.1016/s0006-8993(01)01997-7.Search in Google Scholar PubMed
33. Ding, C, He, Q, Li, P-A. Activation of cell death pathway after a brief period of global ischemia in diabetic and non-diabetic animals. Exp Neurol 2004;188:421–9. https://doi.org/10.1016/j.expneurol.2004.04.013.Search in Google Scholar PubMed
34. Charles, K, Evans, M, Robbins, M, Calver, A, Leslie, R, Pangalos, M. Comparative immunohistochemical localisation of GABAB1a, GABAB1b and GABAB2 subunits in rat brain, spinal cord and dorsal root ganglion. Neuroscience 2001;106:447–67. https://doi.org/10.1016/s0306-4522(01)00296-2.Search in Google Scholar PubMed
35. Fritschy, JM, Meskenaite, V, Weinmann, O, Honer, M, Benke, D, Mohler, H. GABAB‐receptor splice variants GB1a and GB1b in rat brain: developmental regulation, cellular distribution and extrasynaptic localization. Eur J Neurosci 1999;11:761–8. https://doi.org/10.1046/j.1460-9568.1999.00481.x.Search in Google Scholar PubMed
36. Jamal, L, Zhang, H, Finlayson, P, Porter, LA. The level and distribution of the GABABR2 receptor subunit in the rat’s central auditory system. Neuroscience 2011;181:243–56. https://doi.org/10.1016/j.neuroscience.2011.02.050.Search in Google Scholar PubMed
37. Ito, T, Inoue, K, Takada, M. Distribution of glutamatergic, GABAergic, and glycinergic neurons in the auditory pathways of macaque monkeys. Neuroscience 2015;310:128–51. https://doi.org/10.1016/j.neuroscience.2015.09.041.Search in Google Scholar PubMed
38. Venkataraman, Y, Bartlett, EL. Postnatal development of synaptic properties of the GABAergic projection from the inferior colliculus to the auditory thalamus. J Neurophysiol 2013;109:2866–82. https://doi.org/10.1152/jn.00021.2013.Search in Google Scholar PubMed PubMed Central
39. López‐Bendito, G, Shigemoto, R, Kulik, A, Paulsen, O, Fairén, A, Luján, R. Expression and distribution of metabotropic GABA receptor subtypes GABABR1 and GABABR2 during rat neocortical development. Eur J Neurosci 2002;15:1766–78. https://doi.org/10.1046/j.1460-9568.2002.02032.x.Search in Google Scholar PubMed
40. Luyt, K, Slade, TP, Dorward, JJ, Durant, CF, Wu, Y, Shigemoto, R, et al.. Developing oligodendrocytes express functional GABAB receptors that stimulate cell proliferation and migration. J Neurochem 2007;100:822–40. https://doi.org/10.1111/j.1471-4159.2006.04255.x.Search in Google Scholar PubMed
41. Aragno, M, Parola, S, Tamagno, E, Brignardello, E, Manti, R, Danni, O, et al.. Oxidative derangement in rat synaptosomes induced by hyperglycaemia: restorative effect of dehydroepiandrosterone treatment. Biochem Pharmacol 2000;60:389–95. https://doi.org/10.1016/s0006-2952(00)00327-0.Search in Google Scholar PubMed
42. Goto, H, Watanabe, K, Araragi, N, Kageyama, R, Tanaka, K, Kuroki, Y, et al.. The identification and functional implications of human-specific “fixed” amino acid substitutions in the glutamate receptor family. BMC Evol Biol 2009;9:1–10. https://doi.org/10.1186/1471-2148-9-224.Search in Google Scholar PubMed PubMed Central
43. Ito, T, Bishop, DC, Oliver, DL. Expression of glutamate and inhibitory amino acid vesicular transporters in the rodent auditory brainstem. J Comp Neurol 2011;519:316–40. https://doi.org/10.1002/cne.22521.Search in Google Scholar PubMed PubMed Central
44. Prasad, KN, Bondy, SC. Increased oxidative stress, inflammation, and glutamate: potential preventive and therapeutic targets for hearing disorders. Mech Age Dev 2020;185:111191. https://doi.org/10.1016/j.mad.2019.111191.Search in Google Scholar PubMed
45. Faingold, C, Gehlbach, G, Caspary, D. Functional pharmacology of inferior colliculus neurons. Neurobiol Hear Central Audit Syst 1991;2:223–51.Search in Google Scholar
46. Tennigkeit, F, Schwarz, DW, Puil, E. Effects of metabotropic glutamate receptor activation in auditory thalamus. J Neurophysiol 1999;82:718–29. https://doi.org/10.1152/jn.1999.82.2.718.Search in Google Scholar PubMed
47. Voytenko, S, Galazyuk, A. Timing of sound-evoked potentials and spike responses in the inferior colliculus of awake bats. Neuroscience 2008;155:923–36. https://doi.org/10.1016/j.neuroscience.2008.06.031.Search in Google Scholar PubMed PubMed Central
48. Catania, M, Landwehrmeyer, G, Testa, C, Standaert, D, Penney, J, Young, A. Metabotropic glutamate receptors are differentially regulated during development. Neuroscience 1994;61:481–95. https://doi.org/10.1016/0306-4522(94)90428-6.Search in Google Scholar PubMed
49. Martinez-Galan, JR, Perez-Martinez, FC, Juiz, JM. Differences in glutamate-mediated calcium responses in the ventral cochlear nucleus and inferior colliculus of the developing rat. Hear Res 2010;267:46–53. https://doi.org/10.1016/j.heares.2010.03.089.Search in Google Scholar PubMed
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Articles in the same Issue
- Frontmatter
- Reviews
- Covid-19 vaccination and pregnancy: a systematic review of maternal and neonatal outcomes
- Improvised bubble continuous positive airway pressure ventilation use in neonates in resource-limited settings: a systematic review and meta-analysis
- Opinion Papers
- Anger: an underappreciated destructive force in healthcare
- Severe maternal thrombocytopenia and prenatal invasive procedures: still a grey zone
- Commentary
- The care of the magic of life before and after its beginning
- Original Articles – Obstetrics
- The impact of trimester of COVID-19 infection on pregnancy outcomes after recovery
- Adverse outcomes and maternal complications in pregnant women with severe-critical COVID-19: a tertiary center experience
- Are bacteria, fungi, and archaea present in the midtrimester amniotic fluid?
- Bioavailability of the tumor necrosis factor alpha/regulated on activation, normal T cell expressed and secreted (RANTES) biosystem inside the gestational sac during the pre-immune stages of embryo development
- The role of the soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PIGF) – ratio in clinical practice in obstetrics: diagnostic and prognostic value
- Prenatal diagnosis of non-mosaic sex chromosome abnormalities: a 10-year experience from a tertiary referral center
- Prediction of lung maturity through quantitative ultrasound analysis of fetal lung texture in women with diabetes during pregnancy
- Evaluation of an artificial intelligent algorithm (Heartassist™) to automatically assess the quality of second trimester cardiac views: a prospective study
- Original Article – Fetus
- Fetal brain activity and the free energy principle
- Predictive value of ultrasound in prenatal diagnosis of hypospadias: hints for accurate diagnosis
- The effect of maternal diabetes on the expression of gamma-aminobutyric acid and metabotropic glutamate receptors in male newborn rats’ inferior colliculi
- Original Articles – Neonates
- Respiratory function monitoring during early resuscitation and prediction of outcomes in prematurely born infants
- Quality improvement sustainability to decrease utilization drift for therapeutic hypothermia in the NICU
- Short Communication
- Use of a pocket-device point-of-care ultrasound to assess cervical dilation in labor: correlation and patient experience
- Letters to the Editor
- Correspondence on “COVID-19 vaccination and pregnancy”
- Response to the letter to the editor regarding “Covid-19 vaccination and pregnancy: a systematic review of maternal and neonatal outcomes”