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The 30 th Annual Society on Neuroimmune Pharmacology (SNIP) conference will be held on May 3-6 th at the Graduate Hotel by Hilton in Annapolis, Maryland. This 4-day conference will present preclinical, translational, and clinical research in the intersecting fields of neuro-HIV and substance use disorders, as well as related neurodegenerative conditions. The speakers and poster presenters will share cutting-edge research funded by the National Institutes of Health. On the first day, we will have two concurrent preconference symposia. The first is “Single Cell HIV and SUD Effects on the Brain: SCORCH Consortium Progress”, with an overview and 7 presentations by investigators, highlighting the outstanding work in the Single Cell Opioid Response in the Context of HIV (SCORCH). The second concurrent symposium is “Catalyzing Interdisciplinary Research on HIV-Associated Co-occurring Conditions.” In the evening, we will have our first Poster Session with 52 abstracts by early-stage-career investigators (ECIs), including those that received the ECI travel awards. On days 2-4, in addition to a plenary talk and two memorial lectures, we will have 11 symposia, with 62 speakers (including 12 who are early-stage career investigator travel awardees), and 65 additional poster presentations. In total, the 30 th SNIP conference received 185 abstracts for the 70 oral presentations and 115 posters. Topics covered by these symposia and poster presentations include mechanistic and observational studies that evaluate neuronal injury and neuroinflammation associated with HIV brain infection, and how drugs of abuse, including stimulants, opioids, and cannabis, may exacerbate or mitigate neuropathogenesis. In addition, with the aging population of people with HIV and many with substance use disorders, recent work also evaluated how aging and various neurodegenerative disorders could further impact brain health. At the plenary lecture, Dr. Nora Volkow will highlight the priorities of HIV research at the National Institute on Drug Abuse (NIDA), while our banquet speaker, Dr. Avindra Nath will elucidate how viruses, particularly retroviruses, may invade the brain, infect brain cells, and adapt to the local environment for decades or mutate and possibly lead to neurodegenerative disorders. This will be an exciting conference that will continue SNIP’s emphasis on the career development of early-stage investigators.

Objectives In the era of combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is considered a chronic condition that continues to affect the brain. As synaptodendritic injury occurs early, often years before the onset of clinical symptoms, noninvasive neuroimaging methods such as positron emission tomography (PET) hold promise for early detection. Methods A doxycycline (DOX)-inducible HIV-1 Tat 1-86 transgenic mouse model was used to examine the longitudinal impact of Tat expression on synaptic density in vivo. PET imaging with [ 11 C]-UCB-J, a radiotracer targeting synaptic vesicle glycoprotein 2A (SV2A), was performed at 0-, 2-, and 12-weeks after Tat induction via DOX to assess progressive changes in synaptic density in the cerebrum. Complementary Western blot analyses were conducted at 12 weeks of Tat induction to measure SV2A and PSD-95 protein levels across the cortex, prefrontal cortex, striatum, and cerebellum. Results Longitudinal [ 11 C]-UCB-J PET imaging revealed a progressive decline of SV2A in the cerebrum of DOX treated Tat(+) mice compared to Tat(−) controls. Western blot analyses demonstrated a significant genotype x sex interaction in the cortex in which Tat expression reduced SV2A protein levels in females, without affecting males. Further, lower SV2A protein levels were noted overall in males relative to females in the cortex, prefrontal cortex, and cerebellum. No significant effects were detected for PSD-95 protein expression. Conclusions These findings provide in vivo evidence that HIV-1 Tat expression contributes to progressive synaptic density decline and highlight sex-dependent differences in SV2A regulation, supporting SV2A as a biomarker for synaptic alterations in neuroHIV.

Objectives Traumatic brain injury (TBI) is a major cause of mortality and long-term neurological disabilities. Adenosine monophosphate-activated protein kinase (AMPK), a key cellular energy sensor, plays a critical role in maintaining energy homeostasis. Loss of AMPK phosphorylation following TBI impairs the restoration of cellular energy homeostasis and promotes inflammation. In this study, we investigated whether post-TBI loss of AMPK worsens functional impairments, amplifies inflammation, and exacerbates tissue damage in a mouse model of TBI. Methods Adult male C57BL/6 wild-type (WT) and (AMPKα1-KO) mice were subjected to TBI or sham surgery. Behavioral assessments were performed at 24 h post-TBI, followed by mice were anesthetized, and their brains were rapidly collected for histological and biochemical analyses. To further support our findings, mixed glial cells isolated from WT and AMPKα1-KO pups were treated with lipopolysaccharides and interferon-gamma (LI) (0.1 μg/ml LPS and 20 ng/ml IFNg) for 6 h to induce an inflammatory response. Results Our results show that TBI reduces AMPK phosphorylation in WT mice and that AMPK loss correlates with worsened behavioral deficits, enhanced NLRP3 inflammasome activation, and elevated levels of pro-inflammatory mediators, including IL-1β. Similarly, AMPKα1-KO glial cells exhibited greater activation of NLRP3 inflammasome and higher expression of pro-inflammatory markers, such as IL-1β, IL-6, TNF-α, iNOS, and Cox 2, compared with WT cells. Conclusions Collectively, our results demonstrate that AMPKα1 is a critical endogenous regulator of glial-driven neuroinflammation and secondary tissue damage following TBI. Restoring AMPKα1 activity after TBI may therefore represent a promising therapeutic strategy to attenuate neuroinflammation and limit TBI-associated neurological damage.

Objectives With the success of antiretroviral therapy (ART), people with HIV (PWH) are living longer. As they age, they increasingly face age-related comorbidities, including neurodegenerative conditions. The astrocyte–neuron lactate shuttle (ANLS) is a key mechanism that couples astrocytic glycolysis to neuronal oxidative metabolism, ensuring an adequate energy supply for synaptic activity. Disruption of this system has been implicated in both Alzheimer’s disease (AD) and HIV-associated neurocognitive impairment (HIV-NCI), conditions characterized by some overlapping cognitive deficits yet distinct pathological drivers. Methods We investigated the expression of major ANLS transporters, including glucose transporters (GLUT1, GLUT3) and monocarboxylate transporters (MCT1, MCT2, MCT4), in postmortem frontal cortex from individuals with AD and PWH. There were two HIV cohorts based on viral suppression (suppressed/non-suppressed), and both were stratified by neurocognitive status (neurocognitively normal/ neurocognitively impaired), while AD participants were compared to cognitively healthy participants. Quantitative immunoblotting and immunofluorescence imaging characterized disease-specific alterations. Results In AD, both endothelial (GLUT1 55 kDa ) and astrocytic (GLUT1 45 kDa ) isoforms were significantly reduced, along with MCT1, indicating widespread impairment of glucose and lactate transport. GLUT3, the neuronal glucose transporter, also showed a marked reduction. In contrast, in virally non-suppressed (VNS) PWH, GLUT1 45 kDa and MCT4 were downregulated, while virally suppressed (VS) PWH maintained preserved expression. Correlation analyses revealed strong GLUT3–MCT1 coupling in AD, suggestive of coordinated neuronal–astrocytic adaptation, but disrupted GLUT1–MCT4 relationships in VNS PWH, reflecting ANLS uncoupling under viremia. Conclusions These findings identify shared and distinct patterns of metabolic disruption: degeneration-driven ANLS failure in AD versus inflammation-driven uncoupling in HIV-NCI.

Objectives Human immunodeficiency virus 1 (HIV-1)-associated neurocognitive disorders (HAND) persist despite antiretroviral therapy (ART), driven by ongoing neuroinflammation and metabolic dysfunction. This study assesses whether chemical exchange saturation transfer (CEST) MRI can detect HIV-1–induced neurometabolic impairments and ART-mediated improvements in a humanized mouse model. Methods HIV-1–infected CD34-NSG mice underwent CEST MRI at baseline (Week 0), 6 weeks post-infection (6 WPI), and after 6 weeks of ART or vehicle treatment (12 WPI). CEST contrast was quantified at 2 ppm (creatine-related), 3 ppm (glutamate-related), and −3.5 ppm (nuclear Overhauser effect, NOE). Neuroinflammation and infection were evaluated using immunohistochemistry and qPCR. Results At 6 WPI, HIV-1 infection reduced 2-ppm CEST contrast in the cortex and hippocampus and increased NOE in the cortex. By 12 WPI, vehicle-treated mice showed decreased 3-ppm contrast in the cortex, hippocampus, and piriform cortex, whereas ART restored contrast in the cortex and hippocampus. Vehicle-treated mice also showed reduced 2-ppm contrast in the cortex, hippocampus, piriform cortex, and thalamus; ART restored this in the hippocampus, piriform cortex, and thalamus. Increased NOE at −3.5 ppm was observed but did not show measurable improvement following ART. CEST alterations corresponded with decreased HIV-1 p24+ cells and reduced neuroinflammatory markers in ART-treated brains. Conclusions CEST MRI detects region-specific metabolic abnormalities during HIV-1 infection and region-specific metabolic recovery with ART, consistent with reduced viral burden and neuroinflammation. These findings support CEST MRI as a promising non-invasive biomarker for monitoring treatment response and disease progression in neuroHIV.

Human infection with the hepatitis E virus (HEV) is the most common etiology of acute viral hepatitis globally. Estimates are of 20 million cases and 40,000 deaths per year. Researchers in Germany reported in 2009 a new 40–45 % genomic divergent hepevirus species in rats, named Rocahepevirus ratti . Human cases of both acute and chronic hepatitis due to rat HEV (rHEV) were first identified in Hong Kong in 2017. Since then, 49 individuals infected with rHEV have been confirmed worldwide. Herein, we provide an update on the virology, epidemiology, diagnosis, and clinical manifestations of this emerging zoonosis. Specific interventions, including vaccines and antivirals, as ribavirin, are being investigated. Ultimately holistic One Health approaches should be undertaken to confront this new health threat.

Background Early-life opioid exposure can disrupt neurodevelopment and heighten vulnerability to anxiety and affective disorders, particularly in individuals with HIV. Methods Using single-cell RNA sequencing (scRNA-seq), we profiled adolescent brains from wild-type and HIV-1 transgenic (Tg26) female mice exposed to morphine during postnatal days 6–7. Results Morphine exposure in Tg26 mice resulted in a highly dysregulated microglial phenotype, characterized by the ectopic upregulation of genes encoding neuronpeptides ( Avp , Hcrt , and Pmch ), while simultaneously showing a reduction in both inflammatory and homeostatic markers ( Map3k6 , Lgals3 , Ccl3 ). Microglia also showed enhanced expression of dynorphin ( Pdyn ) and κ-opioid receptor ( Oprk1 ) signaling modules implicated in dysphoria and stress-induced negative effects. Furthermore, transcriptomic mapping revealed cell-type-specific neuronal adaptations: cholinergic neurons upregulated genes linked to anxiety and arousal ( Avp , Oxt ), GABAergic neurons upregulated genes linked to condition and aversive behavior, whereas glutamatergic neurons enriched for transcripts associated with thigmotaxis and fear behaviors. Conclusions Together, these findings demonstrate that brief neonatal morphine exposure in an HIV-inflamed milieu induces persistent, cell-type-specific neuroimmune and neurotransmitter reprogramming that engages the dynorphin-KOR pathway and predisposes to anxiety- and aversion-related behaviors.