Molecular Neurobiology最新文献

{"title":"The Role of Cardiolipin in Brain Bioenergetics, Neuroinflammation, and Neurodegeneration.","authors":"Patrick C Bradshaw, Jessa L Aldridge, Leah E Jamerson, Canah McNeal, A Catherine Pearson, Chad R Frasier","doi":"10.1007/s12035-024-04630-6","DOIUrl":"10.1007/s12035-024-04630-6","url":null,"abstract":"<p><p>Cardiolipin (CL) is an essential phospholipid that supports the functions of mitochondrial membrane transporters and oxidative phosphorylation complexes. Due to the high level of fatty acyl chain unsaturation, CL is prone to peroxidation during aging, neurodegenerative disease, stroke, and traumatic brain or spinal cord injury. Therefore, effective therapies that stabilize and preserve CL levels or enhance healthy CL fatty acyl chain remodeling are needed. In the last few years, great strides have been made in determining the mechanisms through which precursors for CL biosynthesis, such as phosphatidic acid (PA), are transferred from the ER to the outer mitochondrial membrane (OMM) and then to the inner mitochondrial membrane (IMM) where CL biosynthesis takes place. Many neurodegenerative disorders show dysfunctional mitochondrial ER contact sites that may perturb PA transport and CL biosynthesis. However, little is currently known on how neuronal mitochondria regulate the synthesis, remodeling, and degradation of CL. This review will focus on recent developments on the role of CL in neurological disorders. Importantly, due to CL species in the brain being more unsaturated and diverse than in other tissues, this review will also identify areas where more research is needed to determine a complete picture of brain and spinal cord CL function so that effective therapeutics can be developed to restore the rates of CL synthesis and remodeling in neurological disorders.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667487","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":"NEFL Modulates NRN1-Mediated Mitochondrial Pathway to Promote Diacetylmorphine-Induced Neuronal Apoptosis.","authors":"Sensen Zhu, Liping Su, Mengjie Zhuang, Li Liu, Min Ji, Jingyu Liu, Chenlu Dai, Jinling Xiao, Yaling Guan, Long Yang, Hongwei Pu","doi":"10.1007/s12035-024-04629-z","DOIUrl":"10.1007/s12035-024-04629-z","url":null,"abstract":"<p><p>Diacetylmorphine abuse is a major social problem that jeopardizes the world, and abuse can cause serious neurological disorders. Apoptosis plays an important role in neurological diseases. A previous study by our group found that the brain tissue of diacetylmorphine-addicted rats showed severe vacuole-like degeneration and increased apoptosis, but the exact mechanism has not yet been reported. We used TMT technology to sequence the diseased brain tissue of rats, and selected neurofilament light chain (NEFL) and neuritin (NRN1) as the focus of our research. We explore the possible roles and mechanisms played by both. Based on the construction of apoptotic cell model, we used overexpression/silencing lentiviral vectors to interfere with the expression of NEFL in PC12 cells, and the results suggested that NEFL could regulate NRN1 to affect the apoptosis level. To further understand the specific mechanism, we used transmission electron microscopy to observe the ultrastructure of apoptotic cells, and the results showed that compared with the control group, mitochondria in the model group showed obvious vacuolation as well as expansion, a significant increase in the accumulation of ROS, and a significant decrease in the mitochondrial membrane potential; after overexpression/silencing of NEFL, these changes were found to occur along with the alteration of NEFL expression. In summary, we conclude that diacetylmorphine induces neuronal apoptosis, and the specific mechanism is that NEFL regulates the NRN1-mediated mitochondrial pathway to promote apoptosis.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667548","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":"GIV/Girdin Modulation of Microglial Activation in Ischemic Stroke: Impact of FTO-Mediated m6A Modification.","authors":"Peng Xie, Mingyan Xia, Tingting Long, Dongfen Guo, Wenpeng Cao, Ping Sun, Wenfeng Yu","doi":"10.1007/s12035-024-04604-8","DOIUrl":"10.1007/s12035-024-04604-8","url":null,"abstract":"<p><p>Ischemic stroke (IS) is one of the most common causes of death in the world. The lack of effective pharmacological treatments for IS was primarily due to a lack of understanding of its pathogenesis. Gα-Interacting vesicle-associated protein (GIV/Girdin) is a multi-modular signal transducer and guanine nucleotide exchange factor that controls important signaling downstream of multiple receptors. The purpose of this study was to investigate the role of GIV in IS. In the present study, we found that GIV is highly expressed in the central nervous system (CNS). GIV protein level was decreased, while GIV transcript level was increased in the middle cerebral artery occlusion reperfusion (MCAO/R) mice model. Additionally, GIV was insensitive lipopolysaccharide (LPS) exposure. Interestingly, we found that GIV overexpression dramatically restrained microglial activation, inflammatory response, and M1 polarization in BV-2 microglia induced by oxygen-glucose deprivation and reoxygenation (OGD/R). On the contrary, GIV knockdown had the opposite impact. Mechanistically, we found that GIV activated the Wnt/β-catenin signaling pathway by interacting with DVL2 (disheveled segment polarity protein 2). Notably, m⁶A demethylase fat mass and obesity-associated protein (FTO) decreased the N6-methyladenosine (m6A) modification-mediated increase of GIV expression and attenuated the inflammatory response in BV-2 stimulated by OGD/R. Taken together, our results demonstrate that GIV inhibited the inflammatory response via activating the Wnt/β-catenin signaling pathway which expression regulated in an FTO-mediated m⁶A modification in IS. These results broaden our understanding of the role of the FTO-GIV axis in IS development.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666692","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":"NF-κB Signaling Pathway in Rheumatoid Arthritis: Mechanisms and Therapeutic Potential.","authors":"Haiyang Liao, Jianxiong Zheng, Jinyue Lu, Hai-Li Shen","doi":"10.1007/s12035-024-04634-2","DOIUrl":"10.1007/s12035-024-04634-2","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease that imposes a heavy economic burden on patients and society. Bone and cartilage destruction is considered an important factor leading to RA, and inflammation, oxidative stress, and mitochondrial dysfunction are closely related to bone erosion and cartilage destruction in RA. Currently, there are limitations in the clinical treatment methods for RA, which urgently necessitates finding new effective treatments for patients. Nuclear transcription factor-κB (NF-κB) is a signaling transcription factor that is widely present in various cells. It plays an important role as a stress source in the cellular environment and regulates gene expression in processes such as immunity, inflammation, cell proliferation, and apoptosis. NF-κB has long been recognized as a pathogenic factor of RA, and its activation can exacerbate RA by promoting inflammation, oxidative stress, mitochondrial dysfunction, and bone destruction. Conversely, inhibiting the activity of the NF-κB pathway effectively inhibits these pathological processes, thereby alleviating RA. Therefore, NF-κB may be a potential therapeutic target for RA. This article describes the physiological structure of NF-κB and its important role in RA through the regulation of oxidative stress, inflammatory response, mitochondrial function, and bone destruction. Meanwhile, we also summarized the impact of NF-κB crosstalk with other signaling pathways on RA and the effect of related drugs or inhibitors targeting NF-κB on RA. The purpose of this article is to provide evidence for the role of NF-κB in RA and to emphasize its significant role in RA by elucidating the mechanisms, so as to provide a theoretical basis for targeting the NF-κB pathway as a treatment for RA.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667469","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":"Mechanism of N6-Methyladenosine Modification in the Pathogenesis of Depression.","authors":"Zhuohang Xian, Liangjing Tian, Zhixuan Yao, Lei Cao, Zhilin Jia, Gangqin Li","doi":"10.1007/s12035-024-04614-6","DOIUrl":"https://doi.org/10.1007/s12035-024-04614-6","url":null,"abstract":"<p><p>N6-methyladenosine (m6A) is one of the most common post-transcriptional RNA modifications, which plays a critical role in various bioprocesses such as immunological processes, stress response, cell self-renewal, and proliferation. The abnormal expression of m6A-related proteins may occur in the central nervous system, affecting neurogenesis, synapse formation, brain development, learning and memory, etc. Accumulating evidence is emerging that dysregulation of m6A contributes to the initiation and progression of psychiatric disorders including depression. Until now, the specific pathogenesis of depression has not been comprehensively clarified, and further investigations are warranted. Stress, inflammation, neurogenesis, and synaptic plasticity have been implicated as possible pathophysiological mechanisms underlying depression, in which m6A is extensively involved. Considering the extensive connections between depression and neurofunction and the critical role of m6A in regulating neurological function, it has been increasingly proposed that m6A may have an important role in the pathogenesis of depression; however, the results and the specific molecular mechanisms of how m6A methylation is involved in major depressive disorder (MDD) were varied and not fully understood. In this review, we describe the underlying molecular mechanisms between m6A and depression from several aspects including inflammation, stress, neuroplasticity including neurogenesis, and brain structure, which contain the interactions of m6A with cytokines, the HPA axis, BDNF, and other biological molecules or mechanisms in detail. Finally, we summarized the perspectives for the improved understanding of the pathogenesis of depression and the development of more effective treatment approaches for this disorder.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648353","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":"Identification and Validation of Oxidative Stress-Related Hub Genes in Parkinson's Disease.","authors":"Lina Zhu, Deng Chen, Xiangxiu Wang, Chengqi He","doi":"10.1007/s12035-024-04622-6","DOIUrl":"https://doi.org/10.1007/s12035-024-04622-6","url":null,"abstract":"<p><p>Accumulating evidence suggests that oxidative stress plays a crucial role in the pathogenesis of Parkinson's disease (PD). The aims of this study were to identify oxidative stress-related hub genes, validate them through the construction of a diagnostic model, explore their interactions with miRNAs and transcription factors (TFs) and predict potential drug targets. Differentially expressed genes (DEGs) in the substantia nigra of PD patients were identified by analyzing a combination of datasets selected from the GEO database, including GSE7621, GSE20141, GSE49036, and GSE20163. The candidate genes associated with oxidative stress were screened by determining the overlap among the DEGs, oxidative stress-related genes (OSGs) and genes in key modules with the highest cor values identified via weighted gene coexpression network analysis (WGCNA). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to perform functional enrichment analysis of these candidate genes. The hub genes were identified via protein-protein interaction (PPI) analysis, and receiver operating characteristic (ROC) curves were constructed to assess the diagnostic value of each hub gene. Then, a diagnostic model was constructed via least absolute shrinkage and selection operator (LASSO) regression with the hub genes identified above, and the model was further validated in external validation datasets (GSE20292 and GSE20164). Gene-miRNA and gene-TF regulatory networks were predicted via the miRNet database, whereas candidate drugs were predicted via the Drug-Gene Interaction database. After analysis of the intersection of the 7975 DEGs, 434 OSGs, and 3582 genes identified through WGCNA, 76 candidate genes were identified. A total of 9 hub genes (JUN, KEAP1, SRC, GPX5, MMP9, TXN, MAPK3, GPX2, and IL1A) were identified via PPI and ROC curve analyses. A diagnostic model with the ability to reliably predict PD on the basis of the identified hub genes (AUC = 0.925) was constructed. Further analysis of these 9 genes revealed 64 targeted miRNAs, 35 TFs in regulatory networks and 86 potential therapeutic agents. Nine hub genes related to oxidative stress in the pathogenesis of PD were identified. These genes show strong diagnostic performance and could serve as therapeutic targets. These findings might facilitate the development of promising candidate biomarkers and potential disease-modifying therapies for PD.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648350","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":"Selective Noradrenergic Activation of BDNF Translation by Mirtazapine.","authors":"Viviana Ciraci, Letizia Santoni, Enrico Tongiorgi","doi":"10.1007/s12035-024-04619-1","DOIUrl":"10.1007/s12035-024-04619-1","url":null,"abstract":"<p><p>Antidepressants are known for their neurotrophic effects, particularly through the regulation of brain-derived neurotrophic factor (BDNF) expression. Mirtazapine, a tetracyclic noradrenergic and specific serotonergic antidepressant (NaSSA) has been observed to upregulate BDNF, though its underlying mechanism remains unclear. In this study, we used the human neuroblastoma SH-SY5Y cell line to investigate whether mirtazapine could enhance BDNF translation by modulating serotonin and/or norepinephrine and their receptors. A 1-h stimulation with 1 or 10 µM mirtazapine led to downregulation of serotonergic receptors 5HT1A, while increasing ADRA2A and ADRB2 receptors. Mirtazapine at 10 µM upregulated endogenous BDNF after 3h, but not 1h stimulation. To investigate the translation of major BDNF transcripts, we used chimeric BDNF-luciferase constructs with the untranslated 5'UTR exons I, IIc, IV, or VI, and the long version of the 3'UTR. Luciferase assays and Western blotting revealed that mirtazapine selectively enhanced exon-IIc-BDNF-long3'UTR-Luciferase translation. This increase was associated with norepinephrine release and was inhibited by blocking ADRA2A or ADRB2 adrenoceptors for the exon-IIc-BDNF-long3'UTR-Luciferase, and ADR2B for endogenous BDNF. These findings provide a new perspective on the critical role of the noradrenergic system in mediating mirtazapine's effects on BDNF translation. We propose a novel mechanism of action in which mirtazapine promotes norepinephrine release and noradrenergic responses by upregulating ADRA2A and ADRB2 while downregulating serotonergic receptors.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667472","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":"Serum Mature and Precursor Brain-Derived Neurotrophic Factors and Their Association with Neurocognitive Function in ART-Naïve Adults Living with HIV in Sub-Saharan Africa.","authors":"Henry U Michael, Antony M Rapulana, Theresa Smit, Njabulo Xulu, Sivapragashini Danaviah, Suvira Ramlall, Frasia Oosthuizen","doi":"10.1007/s12035-024-04599-2","DOIUrl":"https://doi.org/10.1007/s12035-024-04599-2","url":null,"abstract":"<p><p>This study investigates the association between serum mature brain-derived neurotrophic factor (mBDNF), its precursor proBDNF, and neurocognitive function in ART-naïve adults with HIV in sub-Saharan Africa, exploring the distinct roles of these neurotrophic factors in cognitive health. This cross-sectional analysis utilized stored baseline serum samples and neuropsychological test data from participants in the AIDS Clinical Trials Group (ACTG) A5199 study in the Johannesburg and Harare sites. Serum concentrations of mBDNF and proBDNF were quantified using ELISA. Neurocognitive function was assessed via standardized tests, with results adjusted for site-specific demographics. Linear and quantile regression models examined the relationship of mBDNF and proBDNF with a composite cognitive score (NPZ-6), and structural equation modeling (SEM) explored their association with individual cognitive test outcomes. The analysis involved 157 ART-naïve adults with HIV. Increased serum mBDNF levels showed a significant positive association with cognitive performance (β = 1.30, p = 0.02), while elevated proBDNF levels were linked to poorer outcomes, particularly affecting fine motor skills and speed (β =  - 0.29 to - 0.38, p ≤ 0.01). Quantile regression analysis highlighted mBDNF's stronger positive impact at higher cognitive performance percentiles (β = 1.04 (0.01, 2.06) at the 75th percentile), while proBDNF showed significant negative association at the 75th percentile (β =  - 0.26 (- 0.47, - 0.06)). The study highlights the positive association of mature BDNF and the negative association of proBDNF with cognitive function in HIV. These findings emphasize the need for longitudinal research to understand the temporal dynamics of neurotrophic factors during ART initiation and their potential as targets for neurocognitive interventions in HIV.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639319","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":"https://doi.org/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":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-15","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":"Oxidative Stress-mediated Loss of Hippocampal Parvalbumin Interneurons Contributes to Memory Precision Decline After Acute Sleep Deprivation.","authors":"Yu-Zhu Gao, Kai Liu, Xin-Miao Wu, Cui-Na Shi, Qiu-Li He, Hai-Peng Wu, Jian-Jun Yang, Hao Yao, Mu-Huo Ji","doi":"10.1007/s12035-024-04628-0","DOIUrl":"https://doi.org/10.1007/s12035-024-04628-0","url":null,"abstract":"<p><p>Sleep is pivotal to memory consolidation, and sleep deprivation (SD) after learning can impede this process, leading to memory disorders. In the present study, we aimed to explore the effects of acute sleep deprivation (ASD) on memory disorders and the underlying mechanisms. ASD model was induced by subjecting the mice to 6 h of SD following fear conditioning training. Different cohorts were used for behavioral, biochemical, and electrophysiological tests. Here, we showed that memory precision decline was induced by ASD, concomitant with a notable elevation in oxidative stress within PV interneurons, loss of PV, and disturbed neuronal oscillation in the CA1 region. Notably, chemogenetic activation of PV interneurons effectively ameliorated abnormal gamma oscillation and memory precision decline observed in ASD mice. Meanwhile, chemogenetic inhibition of PV interneurons successfully mimicked the abnormal brain oscillations and memory precision decline observed in ASD mice. Additionally, prior administration of the antioxidant medication N-acetylcysteine effectively reversed memory precision decline and mitigated PV loss and abnormal oscillation triggered by ASD. Collectively, our findings indicated that ASD increased oxidative stress in PV interneurons, thereby disrupting neural oscillation in the CA1 and ultimately leading to memory precision decline.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639316","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}