Glia最新文献 - Book学术

Microglial Activation and Inflammatory Responses in Parkinson's Disease Models Are Attenuated by TRPM2 Depletion. 帕金森病模型中的小胶质细胞激活和炎症反应因TRPM2耗竭而减弱

IF 5.1 2区医学

Glia Pub Date : 2025-10-01 Epub Date: 2025-07-15 DOI: 10.1002/glia.70055

Ana Flávia F Ferreira, Zhong-Ping Feng, Hong-Shuo Sun, Luiz Roberto G Britto

{"title":"Microglial Activation and Inflammatory Responses in Parkinson's Disease Models Are Attenuated by TRPM2 Depletion.","authors":"Ana Flávia F Ferreira, Zhong-Ping Feng, Hong-Shuo Sun, Luiz Roberto G Britto","doi":"10.1002/glia.70055","DOIUrl":"10.1002/glia.70055","url":null,"abstract":"Inflammation, and particularly microglial cells, has become a central feature in Parkinson's disease (PD) pathology. The transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable nonselective channel involved in the pathological mechanism of several inflammatory and neurodegenerative diseases. However, the role of TRPM2 in inflammation and microglial activation in the context of PD remains unclear. Here, we combined both in vivo and in vitro PD models to investigate that question. Male and female TRPM2 partial and complete knockout mice were submitted to the 6-hydroxidopamine mouse model of PD. We assessed microglia and lysosome-associated protein (CD68) density levels, microglial morphology and cluster classification, CD68 area in individual microglial cells, and the protein levels of six different cytokines in the substantia nigra pars compacta and the striatum. Our results indicate that TRPM2 deletion reduced microglial density, rescued its morphology, decreased CD68 staining area within microglia, and lowered pro-inflammatory cytokines levels in both male and female mice. To better understand TRPM2 involvement in PD pathology, we selectively knocked-down TRPM2 in neurons, microglia, or both cells in a human neuron-microglia co-culture PD model. An improvement in cell viability and a decrease in cell death were observed across the different experimental approaches. Lastly, TRPM2 deletion revealed reduced microglial phagocytosis and decreased expression of inflammation-related molecules. For the first time, we demonstrated that TRPM2 is a critical mediator of microglial function in the context of PD. Thus, this study suggests that TRPM2 inhibition may offer a novel therapeutic target for PD modification.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":"2035-2056"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Astrocytic-HSP60 Depletion Contributed to Autophagy Defects of Astrocytes and Depressive-Like Behaviors in Male Mice. 星形胶质细胞hsp60缺失导致雄性小鼠星形胶质细胞自噬缺陷和抑郁样行为

IF 5.1 2区医学

Glia Pub Date : 2025-10-01 Epub Date: 2025-07-11 DOI: 10.1002/glia.70060

Weifen Li, Wenhui Zhu, Zi Zhu, Haier Xie, Tahir Ali, Zhijian Yu, Shupeng Li

{"title":"Astrocytic-HSP60 Depletion Contributed to Autophagy Defects of Astrocytes and Depressive-Like Behaviors in Male Mice.","authors":"Weifen Li, Wenhui Zhu, Zi Zhu, Haier Xie, Tahir Ali, Zhijian Yu, Shupeng Li","doi":"10.1002/glia.70060","DOIUrl":"10.1002/glia.70060","url":null,"abstract":"Depression, a prevalent mental health disorder, is multifaceted in its etiology. Growing evidence suggests that dysregulation of heat shock protein 60 (HSP60) contributes to neurological dysfunction, but its role in astrocyte-mediated depressive-like behaviors and neuroinflammation remains poorly understood. Here, we sought to investigate whether astrocyte-specific HSP60 depletion disrupts cellular homeostasis and is associated with astrocyte dysfunction that contributes to depressive-like behaviors and related inflammatory signaling, with a particular emphasis on the role of autophagy. Employing animal models, we demonstrate that chronic stress could dysregulate HSP60 in the brain of mice concurrent with inducing depressive-like symptoms in mice. Furthermore, astrocyte-specific HSP60 depletion (HSP60 cKO) male mice exhibited depressive-like behaviors, alongside significant disruption in astrocyte morphology and impaired autophagic processes within the cortex. Remarkably, these deleterious effects of HSP60 depletion were mitigated by triggering autophagy via urolithin A (UA) treatment, both in the brains of HSP60 cKO mice and in primary astrocytes derived from these mice. These findings shed light on the intricate interplay between astrocytes, HSP60, and autophagy in the etiology of depression, offering potential avenues for therapeutic strategies aimed at modulating astrocytic function and autophagic pathways to alleviate depressive symptoms and astrocyte-associated neuroinflammation.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":"2130-2146"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Shared Lineage, Distinct Outcomes: Yap and Taz Loss Differentially Impact Schwann and Olfactory Ensheathing Cell Development Without Disrupting GnRH-1 Migration. 共享谱系，不同结果：Yap和Taz缺失在不破坏GnRH-1迁移的情况下对雪旺和嗅鞘细胞发育有不同的影响。

IF 5.1 2区医学

Glia Pub Date : 2025-10-01 Epub Date: 2025-07-09 DOI: 10.1002/glia.70057

Ed Zandro M Taroc, Enrico Amato, Alexis M Semon, Nikki Dolphin, Briane Beck, Sophie Belin, Yannick Poitelon, Paolo E Forni

{"title":"Shared Lineage, Distinct Outcomes: Yap and Taz Loss Differentially Impact Schwann and Olfactory Ensheathing Cell Development Without Disrupting GnRH-1 Migration.","authors":"Ed Zandro M Taroc, Enrico Amato, Alexis M Semon, Nikki Dolphin, Briane Beck, Sophie Belin, Yannick Poitelon, Paolo E Forni","doi":"10.1002/glia.70057","DOIUrl":"10.1002/glia.70057","url":null,"abstract":"Olfactory Ensheathing Cells (OECs) are glial cells originating from the neural crest and are critical for bundling olfactory axons to the brain. Their development is crucial for the migration of Gonadotropin-Releasing Hormone-1 (GnRH-1) neurons, which are essential for puberty and fertility. OECs have garnered interest as potential therapeutic targets for central nervous system lesions, although their development is not fully understood. Our single-cell RNA sequencing of mouse embryonic nasal tissues suggests that OECs and Schwann cells share a common origin from Schwann cell precursors yet exhibit significant genetic differences. The transcription factors Yap and Taz have previously been shown to play a crucial role in Schwann cell development. We used Sox10-Cre mice to conditionally ablate Yap and Taz in the migrating neural crest and its derivatives. Our analyses showed reduced Sox10+ glial cells along nerves in the nasal region, altered gene expression in Schwann cells (SCs), melanocytes, and OECs, and a significant reduction in olfactory sensory neurons and vascularization in the vomeronasal organ. However, despite these changes, GnRH-1 neuronal migration remained unaffected. Our findings highlight the importance of the Hippo pathway in OEC development and how changes in cranial neural crest derivatives indirectly impact the development of olfactory epithelia.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":"2077-2097"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diverse Subpopulations of Reactive Astrocytes Following Chronic Toxoplasma Infection. 慢性弓形虫感染后反应性星形细胞的不同亚群。

IF 5.1 2区医学

Glia Pub Date : 2025-10-01 Epub Date: 2025-07-09 DOI: 10.1002/glia.70053

Zoe A Figueroa, Jose L Martin, Arzu Ulu, William Agnew-Svoboda, Teresa Ubina, Martin M Riccomagno, Todd A Fiacco, Emma H Wilson

{"title":"Diverse Subpopulations of Reactive Astrocytes Following Chronic Toxoplasma Infection.","authors":"Zoe A Figueroa, Jose L Martin, Arzu Ulu, William Agnew-Svoboda, Teresa Ubina, Martin M Riccomagno, Todd A Fiacco, Emma H Wilson","doi":"10.1002/glia.70053","DOIUrl":"10.1002/glia.70053","url":null,"abstract":"Astrocytes provide physical and metabolic support for neurons, regulate the blood-brain barrier, and react to injury, infection, and disease. When astrocytes become reactive, maintenance of the inflammatory state and its functional implications throughout chronic neuroinflammation are all poorly understood. Several models of acute inflammation have revealed astrocyte subpopulations that go beyond a two-activation state model, instead encompassing distinct functional subsets. However, how reactive astrocyte (RA) subsets evolve over time during chronic inflammatory disease or infection has been difficult to address. Here we use a prolific human pathogen, Toxoplasma gondii, that causes lifelong infection in the brain alongside a Lcn2CreERT2 reporter mouse line to examine reactive astrocyte subsets during chronic neuroinflammation. Single-cell RNA sequencing revealed diverse astrocyte populations including transcriptionally unique Lcn2CreERT2+ RAs which change over the course of infection in a subset-dependent manner. In addition to an immune-regulating Lcn2CreERT2+ astrocyte population enriched with gene transcripts encoding chemokines CCL5, CXCL9, CXCL10, and receptors CCR7 and IL7R, a specific subset of Lcn2CreERT2+ astrocytes highly expressed transthyretin (Ttr), a secreted carrier protein involved in glycolytic enzyme activation and potential vasculature regulation and angiogenesis. These findings provide novel information about the evolution and diversity of reactive astrocyte subtypes and functional signatures at different stages of infection, revealing an undocumented role for transthyretin-expressing astrocytes in immune regulation at the central nervous system (CNS) vasculature.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":"2003-2024"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Trifluoperazine Elevates Intracellular Ca²⁺ Levels and Locks Open the Store-Operated Calcium Entry Channels in Astrocytes. 三氟拉嗪提高细胞内Ca2+水平并锁开星形胶质细胞储存操作的钙进入通道。

IF 5.1 2区医学

Glia Pub Date : 2025-10-01 Epub Date: 2025-06-16 DOI: 10.1002/glia.70052

Jiwoon Lim, Wongu Youn, C Justin Lee

{"title":"Trifluoperazine Elevates Intracellular Ca2+ Levels and Locks Open the Store-Operated Calcium Entry Channels in Astrocytes.","authors":"Jiwoon Lim, Wongu Youn, C Justin Lee","doi":"10.1002/glia.70052","DOIUrl":"10.1002/glia.70052","url":null,"abstract":"Trifluoperazine (TFP), a known inhibitor of Ca2+-bound calmodulin (Ca2+/CaM), has been reported to elevate cytosolic Ca2+ levels by disinhibiting inositol 1,4,5-triphosphate receptor 2 (IP3R2), thereby suppressing glioblastoma invasion and inducing apoptosis. Interestingly, TFP induces a sustained Ca2+ plateau, sensitive to extracellular Ca2+, suggesting involvement of Ca2+ entry such as store-operated calcium entry (SOCE). However, the underlying molecular mechanism remains elusive. Here, we report that TFP induces sustained Ca2+ signals by blocking the Ca2+/CaM-dependent desensitization of SOCE channels in cortical astrocyte cultures. TFP induces a prolonged Ca2+ response, with distinct kinetics compared to other Ca2+ modulators such as TFLLR-NH2 (a Gαq-coupled GPCR agonist) and thapsigargin (a sacro/endoplasmic reticulum Ca2+-ATPase inhibitor). Under extracellular Ca2+-free conditions, Ca2+ levels increase without reaching a plateau, suggesting that the sustained Ca2+ signal relies on Ca2+ influx. Pharmacological analysis shows that sustained Ca2+ signals by TFP are CaM-dependent. Gene silencing targeting STIM1 and Orai1-3 confirmed their essential roles in the sustained response. We find that TFP effectively \"locks open\" SOCE channels by inhibiting their desensitization, maintaining SOCE activity. This effect is also observed in ex vivo hippocampal dentate gyrus astrocytes. Structural modeling supports a mechanism in which TFP disrupts the interaction between Ca2+/CaM and the SOAR domain of STIM1. Together, these findings indicate that TFP elevates cytosolic Ca2+ levels by maintaining SOCE activation, offering novel insights into the molecular actions of this drug. TFP can be a pharmacological tool for SOCE research as it locks SOCE channels open.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":"1989-2002"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Factors Regulating Oligodendrocyte Progenitor Cell Migration: From Development to Remyelination. 调节少突胶质祖细胞迁移的因素：从发育到髓鞘再生。

IF 5.1 2区医学

Glia Pub Date : 2025-10-01 Epub Date: 2025-06-13 DOI: 10.1002/glia.70051

Ming-Xuan Cao, Johannes Boltze, Shen Li

引用次数: 0

AKT2 Modulates Astrocytic Nicotine Responses In Vivo. AKT2在体内调节星形细胞尼古丁反应

IF 5.1 2区医学

Glia Pub Date : 2025-10-01 Epub Date: 2025-07-15 DOI: 10.1002/glia.70059

Andrew M Lombardi, Mina Griffioen, Helen Wong, Ryan Milstead, Curtis Borski, Erin Shiely, Myra E Bower, Emily Schmitt, Lauren LaPlante, Marissa A Ehringer, Jerry Stitzel, Charles A Hoeffer

{"title":"AKT2 Modulates Astrocytic Nicotine Responses In Vivo.","authors":"Andrew M Lombardi, Mina Griffioen, Helen Wong, Ryan Milstead, Curtis Borski, Erin Shiely, Myra E Bower, Emily Schmitt, Lauren LaPlante, Marissa A Ehringer, Jerry Stitzel, Charles A Hoeffer","doi":"10.1002/glia.70059","DOIUrl":"10.1002/glia.70059","url":null,"abstract":"A greater understanding of the neurobiology of nicotine is needed to reduce or prevent chronic addiction, ameliorate detrimental nicotine withdrawal effects, and improve cessation rates. Nicotine binds and activates two astrocyte-expressed nicotinic acetylcholine receptors (nAChRs), α4β2 and α7. Protein kinase B-β (Pkb-β or Akt2) expression is restricted to astrocytes in mice and humans and is activated by nicotine. To determine if AKT2 plays a role in astrocytic nicotinic responses, we generated astrocyte-specific Akt2 conditional knockout (cKO) and full Akt2 KO mice. For in/ex vivo studies, we examined mice exposed to chronic nicotine for 2 weeks in drinking water (200 μg/mL) or following acute nicotine challenge (0.09, 0.2 mg/kg) after 24 h. Our in vitro studies used cultured mouse astrocytes to measure nicotine-dependent astrocytic responses. Sholl analysis was used to measure glial fibrillary acidic protein responses in astrocytes. Our data show wild-type (WT) mice exhibit increased astrocyte morphological complexity during acute nicotine exposure, with decreasing complexity during chronic nicotine use, whereas Akt2 cKO mice showed enhanced acute responses and reduced area following chronic exposure. In culture, we found 100 μM nicotine sufficient for morphological changes and blocking α7 or α4β2 nAChRs prevented observed morphological changes. We performed conditioned place preference (CPP) in Akt2 cKO mice, which revealed reduced nicotine preference in cKO mice compared to controls. Finally, we performed RNASeq comparing nicotine- and LPS-mediated gene expression, identifying robust differences between these two astrocytic stimuli. These findings show the importance of nAChRs and AKT2 signaling in the astrocytic response to nicotine.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":"2098-2129"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pathways to Progressive Disability in Multiple Sclerosis: The Role of Glial Cells in Chronic CNS Inflammation. 多发性硬化进行性残疾的途径：神经胶质细胞在慢性中枢神经系统炎症中的作用。

IF 5.1 2区医学

Glia Pub Date : 2025-10-01 Epub Date: 2025-05-23 DOI: 10.1002/glia.70044

Volker Siffrin

{"title":"Pathways to Progressive Disability in Multiple Sclerosis: The Role of Glial Cells in Chronic CNS Inflammation.","authors":"Volker Siffrin","doi":"10.1002/glia.70044","DOIUrl":"10.1002/glia.70044","url":null,"abstract":"Multiple sclerosis (MS) is the most common non-infectious inflammatory CNS disease, characterized by progressive neurodegeneration and focal demyelinated lesions. Traditionally considered an autoimmune disease, MS is driven by the immune system's attack on CNS myelin, resulting in cumulative disability. However, conventional anti-inflammatory treatments often fail to prevent progressive deterioration, particularly in the absence of overt inflammation, highlighting the need for a deeper understanding of its pathogenesis. Recent research has revealed a more complex disease mechanism involving both peripheral immune responses and intrinsic CNS factors, with glial cells playing a central role. Persistent inflammation in MS is associated with mixed active/inactive lesions dominated by microglia and astrocyte dysregulation. These glial populations exhibit maladaptive activation, contributing to failed remyelination and ongoing neurodegeneration. Transcriptomic and epigenomic alterations as well as aging further exacerbate glial dysfunction, creating a self-perpetuating cycle of inflammation and damage. Emerging evidence suggests that the interplay between peripheral immune cells and glial populations and the potential dual-use nature of molecular tools shared by the immune system and CNS disrupts homeostatic signaling, leading to a loss of tissue integrity. This review synthesizes findings on glial cell biology in MS, with a focus on microglia and astrocytes, while addressing their roles in demyelination, synapse loss, and neurodegeneration. The limitations of animal models, particularly EAE, in replicating the complexity of MS are also addressed. Finally, critical questions are outlined to guide future research into glial pathology and to identify novel therapeutic approaches targeting progressive MS.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":"1928-1950"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adrenergic Control of P2Y6 Receptor-Dependent Phagocytosis in Rodent and Human Microglia. 鼠和人小胶质细胞中P2Y6受体依赖性吞噬的肾上腺素能调控。

IF 5.1 2区医学

Glia Pub Date : 2025-10-01 Epub Date: 2025-07-15 DOI: 10.1002/glia.70054

Thomas Deluc, Ariel Ase, Marie-France Dorion, Gilles Maussion, Yeman Tang, Rita T M Lo, Irina Shlaifer, Valerio E Piscopo, Thomas M Durcan, Stefano Stifani, Philippe Séguéla

{"title":"Adrenergic Control of P2Y6 Receptor-Dependent Phagocytosis in Rodent and Human Microglia.","authors":"Thomas Deluc, Ariel Ase, Marie-France Dorion, Gilles Maussion, Yeman Tang, Rita T M Lo, Irina Shlaifer, Valerio E Piscopo, Thomas M Durcan, Stefano Stifani, Philippe Séguéla","doi":"10.1002/glia.70054","DOIUrl":"10.1002/glia.70054","url":null,"abstract":"Microglia, the resident immune cells of the central nervous system (CNS), are in constant survey of their environment. Extracellular nucleotides, released by stressed and damaged neurons, act as danger signals to microglia through various purinergic/pyrimidinergic receptors. In the CNS, the UDP receptor P2Y6 is mostly expressed in microglia, where its activation induces phagocytosis, a homeostatic function that is dysregulated in several neurodegenerative diseases and in chronic pain. Yet, modulatory mechanisms impacting P2Y6 activity remain to be identified. The microglial β2 adrenergic receptor (ADRB2) for norepinephrine represents a promising candidate for modulation of P2Y6 receptors. Our calcium imaging data indicate that exposure to the ADRB2 agonist isoproterenol inhibits the calcium transients evoked by activation of Gq-coupled P2Y6 receptors in primary mouse microglia. This functional modulation, suppressed by the selective ADRB2 antagonist ICI-118551, is conserved in human iPSC-derived microglia. Accordingly, we observed that the phagocytotic activity induced by P2Y6 is reduced by ADRB2 signaling in both mouse and human microglia. Finally, we report that ADRB2 activation is linked to a decrease in P2Y6 mRNA expression. These findings provide evidence that metabotropic and transcriptional crosstalks between nucleotide and adrenergic transductions control microglial responses in the CNS, potentially contributing to the pathophysiology of neuro-immune disorders and chronic pain conditions.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":"2025-2034"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Acidic Nanoparticles Prevent HIV Pre-Exposure Prophylaxis (PrEP)-Induced Oligodendrocyte Impairments by Restoring Lysosomal pH in Adolescent Models. 在青少年模型中，酸性纳米颗粒通过恢复溶酶体pH值来预防HIV暴露前预防（PrEP）诱导的少突胶质细胞损伤。

IF 5.1 2区医学

Glia Pub Date : 2025-10-01 Epub Date: 2025-07-17 DOI: 10.1002/glia.70050

Caela C Long, Lindsay K Festa, Melanie Cruz-Berrios, Teshawn D Johnson, Claire H Mitchell, Kelly L Jordan-Sciutto, Judith B Grinspan

{"title":"Acidic Nanoparticles Prevent HIV Pre-Exposure Prophylaxis (PrEP)-Induced Oligodendrocyte Impairments by Restoring Lysosomal pH in Adolescent Models.","authors":"Caela C Long, Lindsay K Festa, Melanie Cruz-Berrios, Teshawn D Johnson, Claire H Mitchell, Kelly L Jordan-Sciutto, Judith B Grinspan","doi":"10.1002/glia.70050","DOIUrl":"10.1002/glia.70050","url":null,"abstract":"A disproportionate percentage of adolescents are diagnosed with human immunodeficiency virus (HIV) in the United States each year. Preexposure prophylaxis (PrEP), an antiretroviral regimen, is effective at preventing the transmission of HIV to adolescents at substantial risk for acquiring HIV. However, other select antiretrovirals have been shown to cause white matter deficits in experimental models. Adolescents taking PrEP are uniquely vulnerable to myelin impairments as the adolescent brain undergoes high rates of myelination. Here, we report that PrEP significantly reduced oligodendrocyte maturation in adolescent rats. Furthermore, cultures of primary rat oligodendrocyte progenitors treated with PrEP showed inhibited oligodendrocyte differentiation through deacidification of lysosomes resulting in lysosomal accumulation of myelin proteins. Acidic nanoparticle co-administration with PrEP prevented PrEP-induced oligodendrocyte maturation impairments both in vivo and in vitro. These studies suggest uninfected adolescents are vulnerable to PrEP-induced oligodendrocyte impairments and identify maintenance of lysosome pH as a critical factor in antiretroviral design.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":"1967-1988"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0