Molecular Neurobiology最新文献

{"title":"Compound-Specific Isotope Analysis as a Potential Approach for Investigation of Cerebral Accumulation of Docosahexaenoic Acid: Previous Milestones and Recent Trends.","authors":"Abdelmoneim H Ali, Mayssa Hachem, Mirja Kaizer Ahmmed","doi":"10.1007/s12035-024-04643-1","DOIUrl":"10.1007/s12035-024-04643-1","url":null,"abstract":"<p><p>Docosahexaenoic acid (DHA, C22:6 n-3), a predominant omega-3 polyunsaturated fatty acid in brain, plays a vital role in cerebral development and exhibits functions with potential therapeutic effects (synaptic function, neurogenesis, brain inflammation regulation) in neurodegenerative diseases. The most common approaches of studying the cerebral accretion and metabolism of DHA involve the use of stable or radiolabeled tracers. Although these methods approved kinetic modeling of ratios and turnovers for fatty acids, they are associated with excessive costs, restrictive studies, and singular dosing effects. Compound-specific isotope analysis (CSIA) is recognized as a cost-effective alternative approach for investigating DHA metabolism in vitro and in vivo. This method involves determining variations in ¹³C content to identify the sources of specific compounds. This review comprehensively discusses a summary of different methods and recent advancements in CSIA application in studying DHA turnover in brain. Following, the ability and applications of CSIA by using gas-chromatography combined with isotope ratio mass-spectrometry to differentiate between natural endogenous DHA in brain and exogenous DHA are also highlighted. In general, the efficiency of CSIA has been demonstrated in utilizing natural ¹³C enrichment to distinguish between the incorporation of newly synthesized or pre-existing DHA into the brain and other body tissues, eliminating the need of tracers. This review provides comprehensive knowledge, which will have potential applications in both academia and industry for advancing the understanding in neurobiology and enhancing the development of nutritional strategies and pharmaceutical interventions targeting brain health.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"5816-5837"},"PeriodicalIF":4.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780598","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}

{"title":"A Neuron-Like Cellular Model for Severe Tinnitus Associated with Rare Variations in the ANK2 Gene.","authors":"Mar Lamolda, Lidia Frejo, Juan Martin-Lagos, Francisca E Cara, Alvaro Gallego-Martinez, Jose A Lopez-Escamez","doi":"10.1007/s12035-024-04674-8","DOIUrl":"10.1007/s12035-024-04674-8","url":null,"abstract":"<p><p>Tinnitus is the perception of sound without an external source, often associated with changes in the auditory pathway and different brain regions. Recent research revealed an overload of missense variants in the ANK2 gene in individuals with severe tinnitus. ANK2, encoding ankyrin-B, regulates axon branching and inhibits microtubule invasion. Missense mutations in ANK2 may promote excessive axonal branching and the formation of excitatory synapses. This study aims to generate a patient-derived iPSC model from an individual with severe tinnitus and to differentiate these cells into otic-neural progenitors and inner ear neurons. We successfully generated a severe tinnitus cellular model through cell reprogramming. Using a two-stage neural differentiation protocol, we differentiated these cells into otic-neural progenitors and neuron-like cells. We confirmed the expression of genes, proteins, and cellular markers, including ANK2, otic-neural progenitors, and neuron-like cells through qPCR and immunostaining. Our analysis revealed higher ANK2 expression in the control cell line compared to the patient cell line. Although both lines formed multipolar neurons, the patient cell line displayed a unique pattern of closely grouped neurons with increased neuronal projections and dendrites compared to the control. This cellular model provides a valuable tool for studying the cellular and molecular changes associated with the ANK2 gene. It holds great promise for the development of novel drug and gene-based therapies for severe tinnitus.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"6467-6477"},"PeriodicalIF":4.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008568","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}

{"title":"PDGFR-α Mediated the Neuroinflammation and Autophagy via the JAK2/STAT3 Signaling Pathway Contributing to Depression-Like Behaviors in Myofascial Pain Syndrome Rats.","authors":"Yu Liu, Feihong Jin, Qinghe Chen, Mingjian Liu, Xuan Li, Lingwei Zhou, Xiaoyue Li, Shaozhong Yang, Feng Qi","doi":"10.1007/s12035-024-04616-4","DOIUrl":"10.1007/s12035-024-04616-4","url":null,"abstract":"<p><p>Depression often occurs in patients with additional co-morbidities, particularly in cases of chronic pain. Currently, there is a lack of research on the molecular mechanisms of depression under chronic pain conditions and suitable animal models. Due to the contradiction exhibited by platelet-derived growth factor receptor (PDGF/PDGFR) in neuroprotection, further investigation is required. In the present study, we investigated the roles of PDGFR-α in the hippocampus based on rat models of chronic pain (myofascial pain syndrome, MPS) that exhibited depressive phenotypes. The depression-like phenotypes were assessed by the sucrose preference test, forced swimming test, tail suspension test, and the levels of BDNF and 5HT1AR. Electron microscopic analysis and altered expression of autophagy-related proteins revealed reduced autophagy levels in the hippocampus of MPS rats. Phosphorylation PDGFR-α was significantly upregulated in the MPS rat model of depression, as well as the levels of inflammatory factors and p-JAK2/p-STAT3. Treatment with inhibitors of PDGFR-α or JAK2/STAT3 alleviated depressive behaviors, Nissl bodies staining, increased the protein levels of BDNF and 5HT1AR, and decreased the levels of inflammatory factors in MPS rats. Additionally, it restored autophagy levels. These results indicate that PDGFR-α induces neuroinflammation, altered autophagy, and depressive behavior, potentially mediated by the JAK2/STAT3 signaling pathway in MPS rats. PDGFR-α may thus represent a promising therapeutic target for the treatment of this type of depression.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"5650-5663"},"PeriodicalIF":4.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142730714","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}

{"title":"Crocin Improves Cognitive Impairment in LPS-treated Rats through Anti-Apoptotic, Anti-Inflammatory, and Antioxidant Activities.","authors":"Maryam Dastan, Ziba Rajaei, Mohammadreza Sharifi, Hossein Salehi","doi":"10.1007/s12035-024-04638-y","DOIUrl":"10.1007/s12035-024-04638-y","url":null,"abstract":"<p><p>Brain inflammation and oxidative stress play critical roles in neuronal apoptosis and memory dysfunction in Alzheimer's disease. Crocin, a natural carotenoid in the stigma of saffron, possesses radical scavenging, anti-inflammatory, and anti-apoptotic properties. This study investigates the protective impact of crocin on neuronal apoptosis, oxidative stress, neuroinflammation, and memory deficits induced by lipopolysaccharide (LPS) in rats. Male Wistar rats received 100 mg/kg of crocin for 12 days, with LPS (1 mg/kg, ip) injected on days 8-12. Spatial learning and memory were evaluated in the Morris water maze two hours after LPS injection. Gene expression of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), caspase 3, and lipid peroxidation was assessed in hippocampal homogenates at the end of the behavioral test. Histopathological changes in the hippocampus and cerebral cortex were evaluated using H&E staining. The results indicated that LPS administration caused spatial learning and memory dysfunction (P = 0.001, P < 0.01) accompanied by upregulation of Nfkb, Tnfα, and Casp3 mRNA expression (P < 0.0001), increased TNF-α (P < 0.01) and lipid peroxidation level (P < 0.01), decreased total thiol concentration (P < 0.05), tissue damage and neuronal loss in the hippocampus (P < 0.0001). Furthermore, crocin treatment at a dosage of 100 mg/kg attenuated learning and memory impairments (P = 0.001, P < 0.01), downregulated Nfkb, Tnfα, and Casp3 mRNA expression (P < 0.0001), decreased TNF-α level (P < 0.01) and lipid peroxidation (P < 0.05) and increased total thiol level (P < 0.05) in the hippocampus. Crocin also ameliorated LPS-induced pathological changes and neuronal loss in the hippocampus (P < 0.001) and cerebral cortex (P < 0.01). In conclusion, the neuroprotective effects of crocin against LPS-induced histopathological and behavioral changes could be attributed to its anti-apoptotic, anti-inflammatory, and radical-scavenging activities in the rat brain.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"5804-5815"},"PeriodicalIF":4.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770521","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}

{"title":"FGF21 Exhibits Neuroprotective Effects by Promoting 5-HT_1AR-FGFR1 Heteroreceptor Complexes and Triggering MEK_1/2-ERK_1/2 Signaling Pathway.","authors":"Qian Yan, Xiao-Jun Li, Qi-Qi Wang, Wei Jia, Shu-Ling Wang","doi":"10.1007/s12035-024-04673-9","DOIUrl":"10.1007/s12035-024-04673-9","url":null,"abstract":"<p><p>Approaches of promoting a neural milieu permissive for plasticity and resilience against neuronal injury are important strategies for the treatment of a range of neurological disorders. Fibroblast growth factor 21 (FGF21) which is known for its role as a potent regulator of glucose and energy metabolism has also proved to be neuroprotective against various mental diseases. However, the underlying molecular mechanisms remain elusive. Here, we report a study of the neuroprotective effects of FGF21 by promoting 5-HT_1AR-FGFR1 heteroreceptor formation and triggering MEK_1/2-ERK_1/2 signaling pathway in normal or abnormal neurological conditions. First, the in vitro cellular experiments demonstrated that FGF21 exerted a protective effect against glutamate-induced cytotoxicity and promoted cell differentiation and growth. Then, in wild-type and FGF21^-/- mice, exogenous FGF21 promoted FGFR1-5-HT_1AR heteromers formation in the CA3 and dentate gyrus region of the hippocampus and activated MEK_1/2-ERK_1/2 signaling. Coordinately, FGF21 exerted similar influences in the hippocampi of IBA-induced neurological injury mice or combined stress-exposed mice. Besides, FGF21 treatment activated the phosphorylation of FGFR1 and elevated the expression of synaptophysin in these mice with neurological injury or combined stress exposure. These results illustrated that FGF21 alleviated neurological impairment through FGFR1-5-HT_1AR heteromer and ERK_1/2 signal activation and suggested that the regulation of FGFR1-5-HT_1AR heteromers and MEK_1/2/ERK_1/2 pathway may play a key role in mediating the neuroprotective effects of FGF21 against various neurodegeneration conditions.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"6369-6382"},"PeriodicalIF":4.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951801","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}

{"title":"Integration of Single-Cell and Spatial Transcriptomic Data Reveals Spatial Architecture and Potential Biomarkers in Alzheimer's Disease.","authors":"Xing Fan, Huamei Li","doi":"10.1007/s12035-024-04617-3","DOIUrl":"10.1007/s12035-024-04617-3","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the gradual loss of neurons and the accumulation of amyloid plaques and neurofibrillary tangles. Despite advancements in the understanding of AD's pathophysiology, the cellular organization and interactions in the prefrontal cortex (PFC) remain elusive. Eight single-cell RNA sequencing (scRNA-seq) datasets from both normal controls and individuals with AD were harmonized. Stringent preprocessing protocols were implemented to uphold dataset integrity. Unsupervised clustering and annotation revealed 22 distinct cell clusters corresponding to 19 unique cell types. The spatial architecture of the PFC region was constructed using the CARD tool. Further analyses encompassed trajectory examination of Oligodendrocyte subtypes, evaluation of regulon activity scores, and spot clustering within white matter regions (WM). Differential expression analysis and functional enrichment assays unveiled molecular signatures linked to AD progression and were validated using microarray data sourced from neurodegenerative disorder patients. Our investigation employs scRNA-seq and spatial transcriptomics to uncover the cellular atlas and spatial architecture of the human PFC in AD. Moreover, our results indicate that Oligodendrocytes are more prevalent in AD patients, showcasing diverse subtypes and spatial organization within WM regions. Each subtype appears to be associated with distinct biological processes and transcriptional regulators, shedding light on their involvement in AD pathology. Notably, the Oligodendrocyte_C6 subtype is linked to neurological damage in AD patients, characterized by heightened expression of genes involved in cell-cell connections, cell membrane stability, and myelination. Additionally, 12 target genes regulated by NFIA were identified, which are upregulated in AD patients and associated with disease progression. Elevated PLXDC2 expression in peripheral blood was also identified, suggesting its potential as a non-invasive biomarker for early AD detection. Our study provides novel insights into the role of Oligodendrocytes in AD and highlights the potential of PLXDC2 as a blood biomarker for non-invasive diagnosis and monitoring of AD patients.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"5395-5412"},"PeriodicalIF":4.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623061","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}

{"title":"Molecular Mechanisms of Spinocerebellar Ataxia Type 17.","authors":"Alina Davidenko, Alexandra Bogomazova, Sergey Illarioshkin, Maria Lagarkova","doi":"10.1007/s12035-024-04645-z","DOIUrl":"10.1007/s12035-024-04645-z","url":null,"abstract":"<p><p>Spinocerebellar ataxia type 17 (SCA17) is a hereditary neurodegenerative disorder characterized by progressive motor and cognitive decline, leading to severe disability and death. SCA17 is caused by a CAG repeat expansion mutation in the TBP gene, resulting in the production of an abnormally long polyglutamine tract, which classifies it as a polyglutamine disorder. At present, there is no effective treatment for SCA17, and existing therapies provide only symptomatic relief. While the exact pathogenic mechanisms of SCA17 remain unclear, the TBP mutation affects a well-characterized transcription factor, making it an ideal model for studying polyglutamine-related neurodegeneration. Here, we review the clinical features of SCA17 and explore proposed mechanisms of its pathogenesis.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"5720-5729"},"PeriodicalIF":4.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770541","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}

{"title":"EHMT2 as a Candidate Gene for an Autosomal Recessive Neurodevelopmental Syndrome.","authors":"Laura Machado Lara Carvalho, Jessica Rzasa, Jennifer Kerkhof, Haley McConkey, Veniamin Fishman, Galina Koksharova, Alexander Augusto de Lima Jorge, Elisa Varella Branco, Danyllo Felipe de Oliveira, Beatriz Martinez-Delgado, Maria J Barrero, Tjitske Kleefstra, Bekim Sadikovic, Luciana Amaral Haddad, Débora Romeo Bertola, Carla Rosenberg, Ana Cristina Victorino Krepischi","doi":"10.1007/s12035-024-04655-x","DOIUrl":"10.1007/s12035-024-04655-x","url":null,"abstract":"<p><p>Neurodevelopmental disorders (NDD) comprise clinical conditions with high genetic heterogeneity and a notable enrichment of genes involved in regulating chromatin structure and function. The EHMT1/2 epigenetic complex plays a crucial role in repression of gene transcription in a highly tissue- and temporal-specific manner. Mutations resulting in heterozygous loss-of-function (LoF) of EHMT1 are implicated in Kleefstra syndrome 1 (KS1). EHMT2 is a gene acting in epigenetic regulation; however, the involvement of mutations in this gene in the etiology of NDDs has not been established thus far. A homozygous EHMT2 LoF variant [(NM_006709.5):c.328 + 2 T > G] was identified by exome sequencing in an adult female patient with a phenotype resembling KS1, presenting with intellectual disability, aggressive behavior, facial dysmorphisms, fused C2-C3 vertebrae, ventricular septal defect, supernumerary nipple, umbilical hernia, and fingers and toes abnormalities. The absence of homozygous LoF EHMT2 variants in population databases underscores the significant negative selection pressure exerted on these variants. In silico evaluation of the effect of the EHMT2(NM_006709.5):c.328 + 2 T > G variant predicted the abolishment of intron 3 splice donor site. However, manual inspection revealed potential cryptic donor splice sites at this EHMT2 region. To directly access the impact of this splice site variant, RNAseq analysis was employed and disclosed the usage of two cryptic donor sites within exon 3 in the patient's blood, which are predicted to result in either an out-of-frame or in-frame effect on the protein. Methylation analysis was conducted on DNA from blood samples using the clinically validated EpiSign assay, which revealed that the patient with the homozygous EHMT2(NM_006709.5):c.328 + 2 T > G splice site variant is conclusively positive for the KS1 episignature. Taken together, clinical, genetic, and epigenetic data pointed to a LoF mechanism for the EHMT2 splice variant and support this gene as a novel candidate for an autosomal recessive Kleefstra-like syndrome. The identification of additional cases with deleterious EHMT2 variants, alongside further functional validation studies, is required to substantiate EHMT2 as a novel NDD gene.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"5977-5989"},"PeriodicalIF":4.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829425","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}

{"title":"Comparative Analysis of Human Brain RNA-seq Reveals the Combined Effects of Ferroptosis and Autophagy on Alzheimer's Disease in Multiple Brain Regions.","authors":"Ke Ye, Xue Zhao, Lulu Liu, Fangliang Ge, Feifei Zheng, Zijie Liu, Mengjie Tian, Xinyu Han, Xu Gao, Qing Xia, Dayong Wang","doi":"10.1007/s12035-024-04642-2","DOIUrl":"10.1007/s12035-024-04642-2","url":null,"abstract":"<p><p>Ferroptosis and autophagy are closely associated with Alzheimer's disease (AD). Elevated ferric ion levels can induce oxidative stress and chronic inflammatory responses, resulting in brain tissue damage and further neurological cell damage. Autophagy in Alzheimer's has a dual role. On one hand, it protects neurons by removing β-amyloid and cellular damage products caused by oxidative stress and inflammation. On the other hand, abnormal autophagy is linked to neuronal apoptosis and neurodegeneration. However, the intricate interplay between ferroptosis and autophagy in AD remains insufficiently explored. This study focuses on the roles of ferroptosis and autophagy in AD and their interconnection through bioinformatics analysis, shedding light on the disease. Ferroptosis and autophagy significantly correlate with the development and course of AD. Using PPI network analysis and unsupervised consistency clustering analysis, we uncovered a complex network of interactions between ferroptosis and autophagy during disease progression, demonstrating a significant congruence in their modification patterns. Functional analyses further demonstrated that ferroptosis and autophagy together affect the immunological status and synaptic regulation in hippocampal regions in patients with AD, which significantly impacts the start and progression of the disease.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"6128-6149"},"PeriodicalIF":4.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876930","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}

{"title":"Novel Perspectives Focused on the Relationship Between Herpesvirus Encephalitis and Anti-GFAP-Antibody-Positive Astrocytopathy.","authors":"Yuqiao Liao, Linxin Wen, Ruoyi Zheng, Yinan Shen, Teng-Ai Ha, Mingkai Lin, Ruogu Cheng, Ye Gao, Pei Shang","doi":"10.1007/s12035-024-04660-0","DOIUrl":"10.1007/s12035-024-04660-0","url":null,"abstract":"<p><p>Virus encephalitis (VE), recognized as one of the common kinds of central nervous system (CNS) diseases after virus infection, has a surprising correlation with autoimmune encephalitis (AE) when autoimmune antibodies emerge in cerebrospinal fluid (CSF) or serum. Herpes simplex virus and Epstein-Barr virus are the most critical agents worldwide. By molecular mimicry, herpes viruses can invade the brain directly or indirectly. As a type-III intermediate filament, glial fibrillary acidic protein (GFAP) can be seen in both the central and peripheral nervous system and is regarded as a marker of astrocyte activation. Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A), an autoimmune inflammatory CNS disorder with unearthed pathogenic mechanism yet, is correlated with CD8 + T cells and AQP4 astrocytopathy in TNF signaling. It brings a new concept of VE and GFAP coexisting, which has been documented in several case reports. Considering the infectious role of herpes viruses in CNS, EBV contributes to GFAP-IgG significantly and may result in GFAP-A. Coincidently, the existence of GFAP-IgG in patients with infection of herpes viruses has been documented as well. There exist multiple diagnoses of VE, ranging from traditional diagnostic criteria, such as CSF examination and electronic techniques, to a novel approach, according to case reports, the detection of GFAP-lgG. In terms of treatment, except for (IVIG), the explorations for new curative targets and optimal diagnostic time are of great necessity. In conclusion, emphasis given to the CNS autoimmune effect brought by the virus infection is highly worthy.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"6179-6194"},"PeriodicalIF":4.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896182","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}