Journal of neuroimmunology最新文献

{"title":"Causal relationships between monocyte chemoattractant protein-1 levels and neuropsychiatric disorders: Evidence from large-scale genetic data","authors":"Yuyao He ,&nbsp;Wenyue Hu ,&nbsp;Yanliang Li ,&nbsp;Zhenyun Han","doi":"10.1016/j.jneuroim.2025.578767","DOIUrl":"10.1016/j.jneuroim.2025.578767","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the causal relationship between monocyte chemoattractant protein-1 (MCP-1) levels and risk of neuropsychiatric disorders (NPDs), including Alzheimer's disease (AD), vascular dementia (VD), depression, schizophrenia (SCZ), and anxiety disorders, using two-sample Mendelian randomization (MR).</div></div><div><h3>Methods</h3><div>Summary statistics from genome-wide association studies (GWAS) were utilized to examine the relationship between MCP-1 levels and NPDs. MCP-1 summary data were obtained from the IEU OpenGWAS database, while GWAS summary statistics for NPDs were primarily sourced from the FinnGen consortium, with additional replication datasets from the IEU OpenGWAS and UK Biobank. The primary analytical approach was the inverse-variance weighted (IVW) method, complemented by weighted median, MR-Egger regression, and both weighted and simple mode methods in bidirectional MR analyses. Heterogeneity was assessed using Cochran's Q test, and horizontal pleiotropy was evaluated using MR-Egger regression and the MR-PRESSO test. Results from multiple GWAS sources were synthesized using meta-analysis to provide robust and comprehensive estimates.</div></div><div><h3>Results</h3><div>In primary MR analysis, IVW results indicated a statistically significant association between elevated MCP-1 levels and increased risk of AD (OR: 1.108; 95 % CI: 1.003–1.224; <em>P</em>_<em>IVW</em> = 0.044) and SCZ (OR: 1.245, 95 % CI: 1.014–1.529, <em>P</em>_<em>IVW</em> = 0.036). No evidence of horizontal pleiotropy was observed (<em>P</em> &gt; 0.05), and leave-one-out sensitivity analysis supported the robustness of these findings. However, no causal associations were identified in replication MR analyses for MCP-1 with any of the NPDs (<em>P</em>_<em>IVW</em> &gt; 0.05). Meta-analysis further confirmed the significant association between MCP-1 levels and AD risk (OR: 1.096, 95 % CI: 1.017–1.182, <em>P</em> = 0.017), while no significant causal relationships were observed for the other NPDs.</div></div><div><h3>Conclusion</h3><div>Elevated MCP-1 levels are causally associated with Alzheimer's disease risk but not with other NPDs, indicating a disease-specific role and therapeutic potential in AD.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578767"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rheumatoid meningitis presented as recurrent stroke-like symptoms: A case report and literature review","authors":"Xin Yang ,&nbsp;Shuping Fang ,&nbsp;Zilong Hao ,&nbsp;Weihong Kuang","doi":"10.1016/j.jneuroim.2025.578763","DOIUrl":"10.1016/j.jneuroim.2025.578763","url":null,"abstract":"<div><h3>Introduction</h3><div>Rheumatoid meningitis (RM) presents a diverse array of symptoms that can mimic stroke or transient ischemic attack (TIA), creating significant challenges for early clinical diagnosis.</div></div><div><h3>Methods</h3><div>This study reported on a patient who presented with recurrent stroke-like symptoms and was diagnosed with RM. Additionally, a literature review was conducted on PubMed using the terms “rheumatoid arthritis,” “central nervous system,” “meningitis,” and “rheumatoid meningitis” on December 20, 2023.</div></div><div><h3>Results</h3><div>Nineteen patients diagnosed with RM who exhibited stroke-like symptoms or TIA were included in the analysis. Of these, 58 % were male, with a median age of 65 years (range: 37–87 years). The duration of rheumatoid arthritis (RA) varied from 0 to 12 years. Approximately 80 % of patients showed meningeal enhancement on MRI, with 47 % displaying asymmetric enhancement, 21 % diffuse enhancement, and 5 % a mass-like lesion. CSF analysis revealed mild elevations in white blood cell count and protein in 68 % of patients. Biopsies were performed in 13 out of 19 cases, with 11 cases (85 %) showing chronic inflammation, including 10 with leptomeningitis or pachymeningitis, 1 with vasculitis, and 1 with necrotizing granulomatous meningitis. Corticosteroids were the most commonly used treatment.</div></div><div><h3>Conclusion</h3><div>For patients presenting with stroke-like or TIA symptoms who have a history of RA, it is crucial to consider RM in the differential diagnosis. Further research is needed to determine the most effective treatment strategies for these patients.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578763"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The missing link: TNF-α as a unifying mechanism in methamphetamine-induced neuronal dysfunction and blood-brain barrier compromise","authors":"Maria Carolina Machado da Silva ,&nbsp;Antônio Carlos Pinheiro de Oliveira ,&nbsp;Eduardo Candelario-Jalil ,&nbsp;Habibeh Khoshbouei","doi":"10.1016/j.jneuroim.2025.578736","DOIUrl":"10.1016/j.jneuroim.2025.578736","url":null,"abstract":"<div><div>Methamphetamine use disorder remains a significant public health concern, impacting neuronal function, immune responses, and vascular integrity. Of particular interest is methamphetamine's disruption of the blood–brain barrier (BBB), a key event that triggers neuroimmune dysfunction and the development of neurodegenerative conditions. While the systemic effects of methamphetamine are well-characterized, the mechanism(s) governing its dysregulation of BBB physiology remain poorly understood. Emerging evidence suggests that the methamphetamine-induced production of tumor necrosis factor (TNF), occurring both in the periphery and within the central nervous system, triggers a cascade of molecular events that compromises BBB permeability. This review provides a comprehensive overview of current findings on the cross interaction between methamphetamine and the BBB, with particular emphasis on the potential role of TNF in dysregulation of BBB permeability and dysfunction. By elucidating the complex interplay between methamphetamine, TNF, and the BBB, we aim to inform the development of targeted interventions and preventative strategies to mitigate methamphetamine-induced neurovascular and neuroimmune dysfunction.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578736"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144989409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in the public IgM repertoire and its idiotypic connectivity in Alzheimer's disease and frontotemporal dementia","authors":"Shina Pashova-Dimova ,&nbsp;Peter Petrov ,&nbsp;Sena Karachanak-Yankova ,&nbsp;Diana Belezhanska ,&nbsp;Yavor Zhelev ,&nbsp;Shima Mehrabian ,&nbsp;Draga Toncheva ,&nbsp;Lachezar Traykov ,&nbsp;Anastas Pashov","doi":"10.1016/j.jneuroim.2025.578775","DOIUrl":"10.1016/j.jneuroim.2025.578775","url":null,"abstract":"<div><div>Alzheimer's disease (AD) and frontotemporal dementia (FTD) are prevalent neurodegenerative disorders. Early diagnosis is challenging due to the lack of definitive biomarkers and reliance on invasive procedures. Immune biomarkers, particularly those reflecting the interaction between the central nervous system (CNS) and the peripheral immune system, have shown promise for non-invasive detection through blood samples. This study investigates the reactivity of serum IgM and IgG from AD and FTD patients against a library of mimotopes representing public IgM reactivities in healthy donors. Serum samples from AD, FTD, and other neurodegenerative dementias (ND) and controls were tested on peptide microarrays. The samples were pooled to mitigate individual variability. The reactivity data were analyzed using graphs to represent the cross-reactivity networks. The analysis revealed distinct reactivity patterns for the studied groups. Public IgM reactivities showed significant correlations with neurodegenerative conditions, with AD and FTD exhibiting loss or gain of specific IgM reactivities. Graph analysis highlighted significant differences between disease and control groups in graph density, clustering, and assortativity parameters. Mimotopes of IgM reactivities lost in dementia, particularly in AD, exhibited significant homology to HCDR3 sequences of human antibodies. Furthermore, clusters of reactivities showed significant distinctions between AD and FTD, with IgG reactivities providing additional differentiation. Several self-proteins related to neurodegeneration proved to have sequences homologous to disease-associated mimotopes. Interestingly, the beta-propeller signature sequence YWTD found in ApoE's receptor LRP1 proved a characteristic epitope for IgG in FTD but not AD. At the same time, the respective public gM mimotope YWTDSSR coincides with a highly conserved sequence in many microorganisms and sequences found in human HCDR3. Thus, the public IgM repertoire, characterized by its broad reactivity and inherent autoreactivity, offers valuable insights into the immunological alterations in neurodegenerative diseases. The study supports the potential of IgM and IgG reactivity profiles as another compartment of non-invasive biomarkers for early diagnosis and differentiating AD and FTD.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578775"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145267109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influenza triggered myositis in an elderly patient: An atypical presentation of influenza infection","authors":"Nayaab Saeed ,&nbsp;Pushpendra Nath Renjen ,&nbsp;Mohd Amaan Mahmood ,&nbsp;Avinash Goswami ,&nbsp;Dinesh Mohan Chaudhari","doi":"10.1016/j.jneuroim.2025.578765","DOIUrl":"10.1016/j.jneuroim.2025.578765","url":null,"abstract":"<div><div>Myositis is characterized by skeletal muscle inflammation and weakness, often accompanied by swelling and muscle pain or tenderness. The etiology could root from autoimmune causes, infective triggers or secondary to systemic diseases. Viral infections are the most widely known cause of infective myositis, among which influenza infection has claimed majority of cases. Here we highlight a case of an unusual but clinically important case of influenza-associated-myositis presenting as an atypical sudden-onset weakness.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578765"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145267112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bortezomib for the treatment of anti-N-methyl-d-aspartate receptor encephalitis in a patient with psoriatic arthritis receiving adalimumab: A case report and literature review","authors":"Lohith Karigowda ,&nbsp;David Brown ,&nbsp;Chong Wong ,&nbsp;Kush Deshpande","doi":"10.1016/j.jneuroim.2025.578754","DOIUrl":"10.1016/j.jneuroim.2025.578754","url":null,"abstract":"<div><div>Anti -<em>N</em>-methyl-<span>d</span>-aspartate receptor antibody (Anti-NMDAR) encephalitis is a serious autoimmune disease that can occur in patients on anti–TNF-α therapy. Adalimumab is a fully human, recombinant monoclonal antibody that inactivates tumour necrosis factor-alpha (TNFα) and is used to treat various autoimmune diseases. The use of Adalimumab has been reported to be associated with autoimmune demyelinating conditions and increases the risk of malignancies. Anti-NMDAR encephalitis associated with anti–TNF-α therapy responds to high-dose corticosteroids, plasma exchange procedures (PLEX), and subsequently, B-cell depletion by the anti-CD20 monoclonal antibody rituximab. A small subset of patients, however, remains refractory to steroids, plasma exchange and rituximab therapy. In these patients, Bortezomib, a proteasome inhibitor, is a potentially effective treatment for those who fail second-line immune therapies.</div><div>Here, we report a case of severe anti-NMDAR encephalitis in a 39-year-old man with psoriatic arthritis who was on Adalimumab treatment for two years before symptom onset. He was refractory to high-dose steroids, plasma exchange, intravenous immunoglobulin (IVIg), and rituximab. Four cycles of Bortezomib were administered 44 days after hospital presentation due to non-resolution of symptoms; following which, we observed gradual neurological recovery, and he was discharged after 94 days of hospital admission. This case demonstrates that Bortezomib may be useful in treating refractory cases of anti-NMDAR encephalitis in patients on Adalimumab.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578754"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145047033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ITPR1 autoantibody-associated autoimmunity as a cause of newly emerging cognitive decline mimicking Alzheimer's disease: Case report and brief review of the literature","authors":"Nicolas Kunath ,&nbsp;Hermod Arne Bollandsås Ramfjord ,&nbsp;Elisabeth Volden Kvisvik ,&nbsp;Marton Konyves-Kolonics ,&nbsp;Gøril Rolfseng Grøntvedt ,&nbsp;Irina I. Serysheva ,&nbsp;Lars Komorowski ,&nbsp;Brigitte Wildemann ,&nbsp;Sven Jarius","doi":"10.1016/j.jneuroim.2025.578774","DOIUrl":"10.1016/j.jneuroim.2025.578774","url":null,"abstract":"<div><h3>Background</h3><div>Since its first description in 2014, anti-inositol 1,4,5-trisphosphate receptor type 1 (ITPR1, also termed IP3R1) autoimmunity has been recognized as causing a clinically heterogeneous spectrum of symptoms. While first described in patients with autoimmune cerebellar ataxia, this facultative paraneoplastic disease has been associated also with peripheral neuropathy, dysautonomia, sleep disorders, neuropsychiatric/psychotic symptoms, and cognitive decline.</div></div><div><h3>Methods</h3><div>Retrospective case study.</div></div><div><h3>Results</h3><div>We report the case of a 58-year-old patient who was admitted with acute confusion, rapidly progressive cognitive decline, and hallucinations. A history of mild cognitive impairment over several years and low cerebrospinal fluid (CSF) amyloid beta-42 and elevated CSF tau protein were suggestive of Alzheimer's disease (AD). However, pleocytosis, intrathecal IgG synthesis and blood-CSF barrier dysfunction prompted screening for antineuronal antibodies, which revealed ITPR1-IgG1/anti-Sj antibodies in both serum and CSF. Brain MRI showed limbic hyperintensities and hippocampal atrophy. No neoplastic disease was found. Immunosuppressive treatment stabilized the disease course but did not lead to symptom improvement.</div></div><div><h3>Conclusions</h3><div>This case underscores the clinical importance of CSF analysis and testing for anti-neural autoantibodies, including less common reactivities, in case of rapid cognitive decline even in patients with known or suspected neurodegenerative disease, such as AD, with ITPR1 representing a novel autoimmune target antigen.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578774"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunological heterogeneity in Ménière's disease: CD4+ T cell subset profiling reveals three distinct Immunophenotypes","authors":"Huaili Jiang ,&nbsp;Yanxia Zhan ,&nbsp;Menglong Zhao ,&nbsp;Shujie Zhang ,&nbsp;Lei Zhou ,&nbsp;Kanglun Jiang ,&nbsp;Yunfeng Cheng ,&nbsp;Xinsheng Huang ,&nbsp;Xiaofeng Xie","doi":"10.1016/j.jneuroim.2025.578743","DOIUrl":"10.1016/j.jneuroim.2025.578743","url":null,"abstract":"<div><h3>Background</h3><div>Ménière's disease (MD) remains a heterogeneous disorder with unclear pathogenesis. While immune dysregulation has been implicated, the specific role of CD4+ T cell subsets and their clinical correlations in MD are poorly understood.</div></div><div><h3>Methods</h3><div>We performed comprehensive immune profiling of 30 MD patients and 27 healthy controls using flow cytometry to analyze six CD4+ T cell subsets (Th1, Th2, Th17, Treg, TGF-β+, TNF-α+) and multiplex cytokine analysis of 16 inflammatory mediators plus IgE. Unsupervised hierarchical clustering identified distinct immune phenotypes, and cox regression analysis determined biomarkers of disease activity.</div></div><div><h3>Results</h3><div>Three distinct immunophenotypes were identified: Autoinflammatory (35.7 %, elevated Th1/TNF-α + cells), inactive (28.6 %, balanced profiles), and type 2-skewed (35.7 %, increased Treg/TGF-β + cells). MD patients showed significantly altered Th1/Th2/Th17 balance with elevated TGF-β + cells (<em>p</em> &lt; 0.001) and decreased serum IFN-γ, IL-1β, and IL-17 a levels, while CCL3/CCL4 chemokines were increased. Cluster-specific immune-clinical correlations revealed distinct pathophysiological patterns. IL-2Rα (HR = 0.18, <em>p</em> = 0.007) and IFN-γ (HR = 0.26, <em>p</em> = 0.046) may represent biomarkers of disease activity.</div></div><div><h3>Conclusion</h3><div>MD exhibits significant immunological heterogeneity with three distinct CD4+ T cell-defined phenotypes. These findings support the development of personalized treatment approaches and suggest potential biomarkers of disease activity, advancing our understanding of MD pathogenesis through comprehensive immune profiling</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578743"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment strategy for myasthenia gravis with GAD65-IgG associated neurological disorders: A case report","authors":"Xiao-Na Xu ,&nbsp;Wen-Jun Luo ,&nbsp;Hui-Ning Li ,&nbsp;Xin Li ,&nbsp;Jun-Ping Wang ,&nbsp;Wei Jiang ,&nbsp;Shu Yang ,&nbsp;Chun-Sheng Yang","doi":"10.1016/j.jneuroim.2025.578741","DOIUrl":"10.1016/j.jneuroim.2025.578741","url":null,"abstract":"<div><div>We present a clinically instructive case of a 50-year-old woman with acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (MG) who subsequently developed glutamic acid decarboxylase 65 (GAD65) antibody-associated neurological disorders alongside a type B2 thymoma. This rare coexistence highlights the profound immune dysregulation induced by thymomas, wherein loss of self-tolerance emergence multiple concurrent autoimmune phenomena. The patient's favorable response to multimodal immunotherapy—including efgartigimod, high-dose corticosteroids, and rituximab—underscores the therapeutic imperative for early, targeted immunomodulation in such complex neuroimmunological syndromes. As no standardized treatment currently exists for MG with GAD65-IgG-associated neurological disorders, this case provides critical clinical insights into both the diagnostic and therapeutic approach for this complex disease.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578741"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The contribution of mTOR to the immunopathology of bipolar disorder","authors":"Amanda Gollo Bertollo ,&nbsp;Vinicius Andrade Jordan ,&nbsp;Milene Zanella Capitanio ,&nbsp;Zuleide Maria Ignácio","doi":"10.1016/j.jneuroim.2025.578744","DOIUrl":"10.1016/j.jneuroim.2025.578744","url":null,"abstract":"<div><div>The mammalian target of rapamycin (mTOR) has a role in immune regulation and neuroplasticity within the brain, influencing various neurological and psychiatric disorders, including bipolar disorder. mTOR signaling, via two complexes, mTORC1 and mTORC2, modulates immune responses by regulating microglial activation, cytokine production, and T-cell function. Dysregulation of these pathways leads to neuroinflammation, a hallmark of several neurological conditions. In bipolar disorder, mTOR affects neuroplasticity by modulating brain-derived neurotrophic factor (BDNF) levels and synaptic remodeling, essential for mood stabilization. Reduced mTOR signaling during depressive episodes and increased activity during manic phases have been observed, with potential links to the cognitive and emotional deficits characteristic of bipolar disorder. This review aims to compile the contribution of mTOR signaling to the immunopathology of bipolar disorder, focusing on its role in immune modulation, neuroinflammation, and neuroplasticity.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578744"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}