NeuroImmune pharmacology and therapeutics最新文献

{"title":"Selective inhibition of TLR2 stimulates the maturation of oligodendroglial progenitor cells to oligodendrocytes.","authors":"Sudipta Chakrabarti, Malabendu Jana, Sukhamoy Gorai, Kalipada Pahan","doi":"10.1515/nipt-2026-0021","DOIUrl":"10.1515/nipt-2026-0021","url":null,"abstract":"<p><p>It is important to describe new technologies for overcoming the barrier and promoting remyelination because many axons remain demyelinated in the CNS of multiple sclerosis (MS) patients. Recent studies indicate that LR2 is a negative regulator of maturation of oligodendroglial progenitor cells (OPCs) to oligodendrocytes (OLs) and that TLR2 is present in human MS chronic lesions. However, until recently, there was no specific inhibitor of TLR2. Therefore, we have engineered a peptide corresponding to the TLR2-interacting domain of MyD88 (TIDM) that specifically inhibits TLR2, but not other TLRs. This study underscores the importance of wild type TIDM (wtTIDM) peptide in promoting the maturation of OPCs to oligodendrocytes. The expression of different maturation markers including PLP, MBP and MOG increased in cultured OPCs in response to wtTIDM, but not mTIDM. While investigating mechanisms, we found that wtTIDM peptide increased the maturation of OPCs isolated from TLR4^-/- mice, but not TLR2^-/- mice, indicating that wtTIDM requires the association with TLR2, but not TLR4, to exhibit this new function. Finally, as evident from double label immunohisto-chemistry and Western blotting, intranasal administration of wtTIDM, but not mTIDM, was capable of increasing OPC maturation and promoting remyelination in the corpus callosum of cuprizone-intoxicated mouse model of demyelination. These results indicate that wtTIDM stimulates the maturation of OPCs via TLR2 and that intranasal wtTIDM may be further evaluated preclinically for stimulating remyelination.</p>","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13577151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal shifts in adaptive immunity drive HIV-associated cryptococcal IRIS: mechanisms, models, and therapeutic opportunities.","authors":"Marcus Hunter, Luis R Martinez","doi":"10.1515/nipt-2026-0016","DOIUrl":"10.1515/nipt-2026-0016","url":null,"abstract":"<p><p>Cryptococcal meningoencephalitis (CME) remains a leading cause of AIDS-related mortality, and up to one-quarter of persons living with HIV who survive CME develop cryptococcal immune reconstitution inflammatory syndrome (CME-IRIS) after antiretroviral therapy (ART) initiation. CME-IRIS arises when recovering immunity encounters a high residual fungal antigen burden, yet the temporal adaptive immune dynamics that distinguish protective reconstitution from damaging neuroinflammation are not fully defined. This review synthesizes clinical and experimental data to propose a temporal framework centered on CD4⁺ T cell polarization, regulatory failure, memory T cell quality, and T-B cell coordination. Before ART, many patients exhibit a Th2-skewed, low-inflammatory state with impaired Th1 responses, reduced antifungal IgM production, and deficient Tfh-B cell coordination, collectively favoring persistent <i>Cryptococcus neoformans</i> antigen burden. With ART, IL-7-driven T cell recovery, Th17/Treg imbalance, Th1/Th17-biased memory responses, and chemokine-guided trafficking of CXCR3⁺CCR5⁺ effector cells into the central nervous system can convert this antigen-rich milieu into fulminant neuroinflammation. We further discuss emerging mouse models that recapitulate unmasking CME-IRIS, the contrasting immune profile of <i>Cryptococcus gattii</i>-associated IRIS as a comparative model, and developing therapeutic strategies that include targeted immunomodulators, cell-based therapies, and vaccines. Finally, we highlight future directions - particularly single-cell and spatial transcriptomic profiling of blood and CSF - to resolve which adaptive immune populations drive neuroinflammation and to validate predictive biomarkers for CME-IRIS. A temporally informed view of adaptive immunity in CME-IRIS may refine ART timing, guide risk stratification, and identify new adjunctive interventions for cryptococcosis and related IRIS syndromes.</p>","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13477641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methamphetamine enhances HIV infection of human iPSC-derived microglia.","authors":"Xiao-Long Wang, Xu Wang, Yuan Rong, Wen-Zhe Ho","doi":"10.1515/nipt-2026-0003","DOIUrl":"10.1515/nipt-2026-0003","url":null,"abstract":"<p><p>Methamphetamine (METH) is a potent psychostimulant that is commonly used by people infected with HIV. Clinically, METH use is implicated in HIV infection and neuroinflammation. In this study, we examined whether METH has direct effect on HIV infection of human microglia, the major target and reservoir cells for the virus in the brain. We observed that METH treatment of human iPSC-derived microglia (iMg) significantly enhanced HIV replication, as indicated by increased HIV gag expression, p24 protein levels, and reverse transcriptase activity. Mechanistically, METH suppressed the expression of interferons (IFNs), IFN stimulated gene (Viperin) and the CC chemokine (RANTES). In addition, METH upregulated the expression of the HIV entry coreceptors (CCR5 and CXCR4) in iMg. These findings suggest that METH use is a promoting factor for HIV infection of microglia. Because many individuals infected with HIV use METH, it is important to further investigate the interactions between METH use and HIV in target cells to better understand the mechanisms underlying HIV persistence in the brain and to develop effective strategies for viral eradication.</p>","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"5 2","pages":"265-269"},"PeriodicalIF":0.0,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13544641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148898625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PPARα and RXRα in the regulation of neuronal ceroid lipofuscinosis genes: implications for Batten disease therapy.","authors":"Sujyoti Chandra, Kalipada Pahan","doi":"10.1515/nipt-2026-0005","DOIUrl":"10.1515/nipt-2026-0005","url":null,"abstract":"<p><p>Neuronal ceroid lipofuscinosis or Batten disease comprises a category of autosomal recessive neurodegenerative disorders that primarily affect children. Mutations in different genes lead to different forms of neuronal ceroid lipofuscinoses (CLN1-14). At present, there is no established therapy to cure most of the neuronal ceroid lipofuscinoses and the treatments are symptomatic. Enzyme replacement therapy, gene therapy, stem cell transplantation, and pharmacological chaperone therapy are being tested in different animal models and human patients. Peroxisome proliferator-activated receptor alpha (PPARα) is a member of the nuclear hormone receptor superfamily, which along with its transcription partner retinoid X receptor alpha (RXRα) regulates the expression of their target genes. This review highlights the potential role of PPARα and RXRα in the regulation of <i>CLN</i> genes. Here, using the MatInspector program of the Genomatix software, we performed promoter analyses of all <i>CLN</i> genes and observed that most of the <i>CLN</i> genes harbor one or more potential binding sites for PPAR and RXR in their promoter region. We further grouped them according to a binding prediction of the transcription factors to indicate high affinity binding of PPAR to <i>CLN2</i>, <i>CLN3</i>, <i>CLN4</i>, <i>CLN5, CLN7</i>, <i>CLN10</i>, <i>CLN11</i>, <i>CLN12</i>, and <i>CLN14</i>. On the other hand, we observed high affinity binding of RXR to <i>CLN1</i>, <i>CLN3</i>, <i>CLN6</i>, <i>CLN7</i>, <i>CLN8</i>, <i>CLN10</i>, and <i>CLN13</i>. Since PPARα and RXRα have been demonstrated to control the transcription of <i>CLN2</i> gene, our current promoter analysis findings highlight a possible treatment strategy for neuronal ceroid lipofuscinoses using agonists of PPARα and RXRα.</p>","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13178501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147965857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 30^th Scientific Conference of the Society on NeuroImmune Pharmacology in Annapolis, Maryland, May 3^rd - 6^th, 2026.","authors":"Linda Chang, Susmita Sil, Jerel Adam Fields, Allison Andrews, Servio Ramirez, Richard Noel","doi":"10.1515/nipt-2026-0006","DOIUrl":"10.1515/nipt-2026-0006","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"5 1","pages":"1-77"},"PeriodicalIF":0.0,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of AMPK potentiates inflammation by activating the infammasome in a preclinical mouse model of TBI.","authors":"Mohammad Ejaz Ahmed, Hamid Suhail, Mohammad Nematullah, Benoit Viollet, Shailendra Giri, Abdullah Shafique Ahmad","doi":"10.1515/nipt-2024-0019","DOIUrl":"10.1515/nipt-2024-0019","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147596605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIV-1 Tat expression drives progressive synaptic decline: evidence from longitudinal [¹¹C]-UCB-J PET imaging.","authors":"Tara Chand Yadav, Isabella C Orsucci, Spencer V Thompson, Zhanhong Wu, Zibo Li, Hong Yuan, Barkha J Yadav-Samudrala, Sylvia Fitting","doi":"10.1515/nipt-2025-0020","DOIUrl":"10.1515/nipt-2025-0020","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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 <i>in vivo.</i> PET imaging with [¹¹C]-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.</p><p><strong>Results: </strong>Longitudinal [¹¹C]-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.</p><p><strong>Conclusions: </strong>These findings provide <i>in vivo</i> 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.</p>","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"5 1","pages":"79-92"},"PeriodicalIF":0.0,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analyses of astrocyte-neuron lactate shuttle transporter levels in brain tissues from people with HIV-associated neurocognitive impairment and Alzheimer's disease.","authors":"Ali Boustani, Anna Laird, Leeann Shu, Erin E Sundermann, David J Moore, Robert Rissman, Jerel A Fields","doi":"10.1515/nipt-2025-0019","DOIUrl":"10.1515/nipt-2025-0019","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>These findings identify shared and distinct patterns of metabolic disruption: degeneration-driven ANLS failure in AD versus inflammation-driven uncoupling in HIV-NCI.</p>","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12945393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CEST MRI assessment of HIV-1-associated neurometabolic impairments in a humanized mouse model.","authors":"Gabriel C Gauthier, Micah Summerlin, Balasrinivasa R Sajja, Mariano G Uberti, Emma G Foster, Manjeet Kumar, Matthew Thiele, Santhi Gorantla, Aditya N Bade, Yutong Liu","doi":"10.1515/nipt-2025-0017","DOIUrl":"10.1515/nipt-2025-0017","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12920017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147273443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S-Equol: a novel therapeutic for HIV-1-associated gastrointestinal dysbiosis.","authors":"Mason T Rodriguez, Sarah J Olmstead, Kristen A McLaurin, Charles F Mactutus, Rosemarie M Booze","doi":"10.1515/nipt-2024-0024","DOIUrl":"10.1515/nipt-2024-0024","url":null,"abstract":"<p><strong>Objective: </strong>HIV-1 infection affects approximately 38.4 million people around the world. The advent of combination anti-retroviral therapy (cART) has greatly improved the quality of life of infected individuals; however, roughly 50 % of these individuals will still experience HIV-1-associated neurocognitive disorders (HAND). Additionally, the gastrointestinal microbiome has been reported to be dysbiotic in HIV-1 infected individuals, regardless of adherence to cART. Current research has pointed to the gut-brain-microbiota axis as a potential target to treat both cognitive deficits and microbial changes. The present study investigated S-Equol (SE) as a potential therapeutic for HAND by modulating the gastrointestinal microbiome.</p><p><strong>Methods: </strong>The study included 21 HIV-1 Tg rats and 21 F344 control animals to test the effect 0.2 mg SE has on cocaine-maintained responding on a PR schedule of reinforcement.</p><p><strong>Results: </strong>Gastrointestinal microbiome alterations between genotypes were found at the phylum and genus level, regardless of treatment group, and SE treatment had both main effects and interactions with genotype. <i>Prevotella_UCG_001</i> was significantly associated with lever presses for drug, suggesting an effect on motivation for cocaine. <i>Alloprevotella</i> was found to significantly differentiate between genotype by treatment effects, indicating that SE differently affects genotypes.</p><p><strong>Conclusions: </strong>SE may provide a novel adjuvant treatment in addition to cART for HIV-1-associated dysbiosis and associated neurocognitive dysfunction.</p>","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"4 4","pages":"325-337"},"PeriodicalIF":0.0,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12755389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}