Journal of Molecular Neuroscience最新文献

{"title":"The Potential of cfDNA as Biomarker: Opportunities and Challenges for Neurodegenerative Diseases","authors":"Şeyma Aydın,&nbsp;Selçuk Özdemir,&nbsp;Ahmet Adıgüzel","doi":"10.1007/s12031-025-02317-8","DOIUrl":"10.1007/s12031-025-02317-8","url":null,"abstract":"<div><p>Neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), are characterized by the progressive and gradual degeneration of neurons. The prevalence and rates of these disorders rise significantly with age. As life spans continue to increase in many countries, the number of cases is expected to grow in the foreseeable future. Early and precise diagnosis, along with appropriate surveillance, continues to pose a challenge. The high heterogeneity of neurodegenerative diseases calls for more accurate and definitive biomarkers to improve clinical therapy. Cell-free DNA (cfDNA), including fragmented DNA released into bodily fluids via apoptosis, necrosis, or active secretion, has emerged as a promising non-invasive diagnostic tool for various disorders including neurodegenerative diseases. cfDNA can serve as an indicator of ongoing cellular damage and mortality, including neuronal loss, and may provide valuable insights into disease processes, progression, and therapeutic responses. This review will first cover the key aspects of cfDNA and then examine recent advances in its potential use as a biomarker for neurodegenerative disorders.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-025-02317-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Extracellular Matrix Protein 2 Level as a Predictive Biomarker for Rupture of Small Intracranial Aneurysms","authors":"Chenchen Wang,&nbsp;Yuwei Han,&nbsp;Da Huo,&nbsp;Xiaoming Li,&nbsp;Guobiao Liang","doi":"10.1007/s12031-024-02305-4","DOIUrl":"10.1007/s12031-024-02305-4","url":null,"abstract":"<div><p>As the neuroimaging technology improves, the detection rate of unruptured intracranial aneurysms (UIA) is gradually increasing. However, there is currently no effective means to evaluate and predict the risk of rupture for small intracranial aneurysm (sIA, diameter &lt; 7 mm). We previously identified extracellular matrix protein 2 (ECM2) as a potential candidate biomarker for predicting intracranial aneurysm (IA) rupture through iTRAQ combined with LC–MS/MS protein quantification technology, so this study aimed to further validate the ability of plasma ECM2 expression levels to predict IA rupture. This prospective, observational, single-center cohort study enrolled 322 individuals with ruptured intracranial aneurysm (RIA, <i>N</i> = 123), UIA (<i>N</i> = 89), traumatic subarachnoid hemorrhage (tSAH, <i>N</i> = 55), or healthy controls (HC, <i>N</i> = 55). ECM2 plasma levels were quantified using enzyme-linked immunosorbent assay (ELISA). The Spearman rank correlation analysis was employed to examine the relationship between variables. Independent risk factors of sIA rupture were identified using logistic regression analysis. The ROC curve assessed the predictive capability for sIA rupture. Plasma ECM2 was notably higher in RIA patients than in UIA, tSAH, and HC groups. Plasma ECM2 levels showed no significant difference among the asymptomatic UIA, HC, and tSAH groups. There was also no significant difference in plasma ECM2 levels between symptomatic UIA patients and RIA patients. Furthermore, the plasma ECM2 level was closely related to hypertension history in sIA patients. ECM2 plasma level was an independent risk factor for sIA rupture. The plasma ECM2 cutoff level for predicting IA rupture was determined to be 1540.67 pg/ml. The combination of ECM2 levels and aneurysm location increased predictive accuracy (AUC = 0.828, sensitivity 87.0%, specificity 68.8%, accuracy 83.2%), surpassing the performance of PHASES and ELPASS scores. ECM2 could potentially act as an early warning biomarker for predicting the rupture of sIAs.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602433","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":"Temporal Transcriptomic Differences in Stroke Between Diabetic and Non-Diabetic Mice","authors":"Yifei Lv,&nbsp;Xiaomin Dong,&nbsp;Yujie Xi,&nbsp;Fang Zhan,&nbsp;Yining Mao,&nbsp;Jianhua Wu,&nbsp;Xiaoyan Wu","doi":"10.1007/s12031-025-02327-6","DOIUrl":"10.1007/s12031-025-02327-6","url":null,"abstract":"<div><p>Diabetes is a key risk factor for ischemic stroke and negatively impacts long-term outcomes post-stroke. However, genomic studies on diabetic stroke remain insufficient. This study aims to investigate the interaction between diabetes and stroke from the acute phase to the early recovery phase by establishing a diabetic stroke animal model and comparing transcriptome sequencing results with those of non-diabetic stroke models. The study identified a greater number of downregulated genes in the diabetic stroke group compared to the non-diabetic group at different stages post-stroke. Functional enrichment analysis revealed an enhanced immune response and a relatively lower neurodegeneration potential in the diabetic group. Post-stroke, a higher presence of CD4 + T cells, eosinophils, and M1 macrophages was observed in the diabetic group. Additionally, time-series analysis identified a set of genes with time-specific expression patterns following diabetic stroke. This study underscores the role of inflammation and immune responses as potential factors exacerbating ischemic stroke in diabetes while also identifying gene regulatory networks at different stages post-stroke. These findings provide new insights into the role of diabetes in stroke and suggest potential therapeutic targets for improving outcomes in diabetic patients.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571004","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":"Discovery of Novel Protein-Coding and Long Non-coding Transcripts in Distinct Regions of the Human Brain","authors":"Kristina Santucci,&nbsp;Yuning Cheng,&nbsp;Si-Mei Xu,&nbsp;Yulan Gao,&nbsp;Grace Lindner,&nbsp;Konii Takenaka,&nbsp;Michael Janitz","doi":"10.1007/s12031-025-02316-9","DOIUrl":"10.1007/s12031-025-02316-9","url":null,"abstract":"<div><p>Recent improvements in the accuracy of long-read sequencing (LRS) technologies have expanded the scope for novel transcriptional isoform discovery. Additionally, these advancements have improved the precision of transcript quantification, enabling a more accurate reconstruction of complex splicing patterns and transcriptomes. Thus, this project aims to take advantage of these analytical developments for the discovery and analysis of RNA isoforms in the human brain. A set of novel transcript isoforms was compiled using three bioinformatic tools, quantifying their expression across eight replicates of the cerebellar hemisphere, five replicates of the frontal cortex, and six replicates of the putamen. By taking a subset of the novel isoforms consistent across all discovery methods, a set of 170 highly confident novel RNA isoforms was curated for downstream analysis. This set consisted of 104 messenger RNAs (mRNAs) and 66 long non-coding RNAs (lncRNAs) isoforms. The detailed structure, expression, and potential encoded proteins of novel mRNA isoform BambuTx321 have been further described as an exemplary representative. Additionally, the tissue-specific expression [mean counts per million (CPM) of 5.979] of novel lncRNA, BambuTx1299, in the cerebellar hemisphere was observed. Overall, this project has identified and annotated several novel RNA isoforms across diverse tissues of the human brain, providing insights into their expression patterns and investigating their potential functional roles. Thus, this project has contributed to a more comprehensive understanding of the brain’s transcriptomic landscape for applications in basic research.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-025-02316-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143553787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights Into the Therapeutic Potential of SIRT1-modifying Compounds for Alzheimer’s Disease: A Focus on Molecular Mechanisms","authors":"Dhyauldeen Aftan AlHayani,&nbsp;Aziz Kubaev,&nbsp;Subasini Uthirapathy,&nbsp;Viralkumar Mandaliya,&nbsp;Suhas Ballal,&nbsp;Rishiv Kalia,&nbsp;Renu Arya,&nbsp;Baneen C. Gabble,&nbsp;Mohammed Qasim Alasheqi,&nbsp;Abed J. Kadhim","doi":"10.1007/s12031-025-02324-9","DOIUrl":"10.1007/s12031-025-02324-9","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss, significantly impacting patients’ quality of life. Recent studies have highlighted the roles of sirtuin 1 (SIRT1), a NAD + -dependent deacetylase, in regulating various biological pathways associated with AD pathology, including amyloid-beta metabolism, tau hyperphosphorylation, and neuroinflammation. This review focuses on the therapeutic potential of synthetic and natural compounds that modulate SIRT1 levels, emphasizing their molecular mechanisms of action. We explore a range of SIRT1-modifying agents, including polyphenols such as resveratrol, as well as synthetic analogs and novel pharmaceuticals that aim to enhance SIRT1 activity. Additionally, we discuss emerging innovative therapies, including pharmacological agents that improve SIRT1 signaling through mechanisms like photobiomodulation and nutritional interventions. These compounds not only target SIRT1 but also integrate into broader metabolic and neuroprotective pathways, presenting a promising approach to ameliorating AD symptoms. By elucidating the intricate interactions between SIRT1-modifying compounds and their effects on AD pathology, this review aims to advance the understanding of potential therapeutic strategies that could delay or prevent the progression of AD.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489553","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":"Malformations of Core M3 on α-Dystroglycan Are the Leading Cause of Dystroglycanopathies","authors":"Wessam Sharaf-Eldin","doi":"10.1007/s12031-025-02320-z","DOIUrl":"10.1007/s12031-025-02320-z","url":null,"abstract":"<div><p>Dystroglycanopathies (DGPs) are a group of autosomal recessive neuromuscular diseases with significant clinical and genetic heterogeneity. They originate due to defects in the O-mannosyl glycosylation of α-dystroglycan (α-DG), a prominent linker between the intracellular cytoskeleton and the extracellular matrix (ECM). Fundamentally, such interactions are crucial for the integrity of muscle fibers and neuromuscular synapses, where their defects are mainly associated with muscle and brain dysfunction. To date, biallelic variants in 18 genes have been associated with DGPs, where the underlying cause is still undefined in a significant proportion of patients. Glycosylation of α-DG generates three core motifs where the core M3 is responsible for interaction with the basement membrane. Consistently, all gene defects that corrupt core M3 maturation have been identified as causes of DGPs. <i>POMGNT1</i> which stimulates the generation of core M1 is also associated with DGPs, as it plays a central role in core M3 processing. Other genes involved in the glycosylation of α-DG seem unrelated to DPGs. The current review illustrates the <i>O</i>-mannosylation pathway of α-DG highlighting the functional properties of related genes and their contribution to the progression of DPGs. Different classes of DPGs are also elaborated characterizing the clinical features of each distinct type and phenotypes associated with each single gene. Finally, current therapeutic approaches with favorable outcomes are addressed. Potential achievements of preclinical and clinical studies would introduce effective curative therapies for this group of disorders in the near future.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-025-02320-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Interaction of ATG7 and Plasma Metal Concentrations on Cognitive Impairment in Rural China","authors":"Xu Tang,&nbsp;Jiejing Cao,&nbsp;Jiansheng Cai,&nbsp;Xiaoting Mo,&nbsp;Yanfei Wei,&nbsp;Kailian He,&nbsp;Zeyan Ye,&nbsp;Yu Jian Liang,&nbsp;Linhai Zhao,&nbsp;Lidong Qin,&nbsp;You Li,&nbsp;Jian Qin,&nbsp;Zhiyong Zhang","doi":"10.1007/s12031-025-02322-x","DOIUrl":"10.1007/s12031-025-02322-x","url":null,"abstract":"<div><p>The objective of this study is to explore the association of plasma metal concentrations with impaired cognitive function in different genotypes of ATG7 using multiple models. A cross-sectional survey was conducted in rural China among 994 individuals aged 30 years or older. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Genetic analysis focused on two single-nucleotide polymorphisms (SNPs) in the autophagy-related gene ATG7 (rs2606757 and rs8154). Plasma concentrations of metals were quantified using inductively coupled plasma mass spectrometry. Restricted cubic splines were used to explore the association between serum metal concentration and the occurrence of mild cognitive impairment in individuals with various genotypes. Bayesian Kernel Machine Regression (BKMR) models were used to explore the interactions between individual metals. In a restricted cubic spline model, there is a nonlinear relationship between plasma concentration of Cd and the occurrence of cognitive impairment in individuals carrying the AA (<i>P</i> of Nonlinear = 0.008) and AT (<i>P</i> of Nonlinear = 0.007) genotypes at the rs2606757. However, in people carrying the TT genotype at the rs2606757 locus, the concentration of metals in plasma was not significantly associated with cognitive impairment (<i>P</i> of Nonlinear = 0.534). The results of the BKMR model are consistent with those of the restricted cubic spline model. The TT genotype at rs2606757 in ATG7 appears to confer greater cognitive resilience against Cd-induced cognitive damage. These findings highlight the importance of considering gene-environment interactions in the context of cognitive impairment and suggest potential avenues for preventing cognitive decline in individuals exposed to Cd. Further research is needed to elucidate the precise mechanisms underlying these interactions.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475261","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":"SOX10-Mediated Regulation of Enteric Glial Phenotype in vitro and its Relevance for Neuroinflammatory Disorders","authors":"Madlen Kunke,&nbsp;Meike Kaehler,&nbsp;Sebastien Boni,&nbsp;Katja Schröder,&nbsp;Alicia Weier,&nbsp;Rittika Chunder,&nbsp;Stefanie Kuerten,&nbsp;Martina Böttner,&nbsp;Ingolf Cascorbi,&nbsp;Michel Neunlist,&nbsp;Thilo Wedel,&nbsp;Ralph Lucius,&nbsp;François Cossais","doi":"10.1007/s12031-025-02321-y","DOIUrl":"10.1007/s12031-025-02321-y","url":null,"abstract":"<p>The transcription factor SOX10 is a key regulator of myelinated glial cell phenotype and function, with a known role in multiple sclerosis (MS). SOX10 is also expressed in enteric glial cells (EGC) within the gut, yet its regulatory functions in EGC remain poorly understood. This study aimed to identify SOX10 target genes that influence EGC phenotype and may have implications for MS. An EGC cell line was established for doxycycline-inducible SOX10 overexpression. Impact of SOX10 overexpression on EGC phenotype was assessed by genome-wide expression analysis and results were validated via RT-qPCR and western blot. Data were compared with SOX10 ChIP-seq and transcriptomic datasets from MS patients to identify pan-glial SOX10 target genes potentially linked to neuroinflammatory disorders. SOX10 overexpression was associated with ectopic upregulation of genes related to myelin regulation and glial differentiation, as evidenced by increased PLP1 expression at mRNA and protein levels. Comparison to ChIP-seq and MS datasets highlight SOX10 target genes, including <i>PLP1</i>, <i>RNF130</i>, <i>NES</i> and <i>APOD</i> potentially involved in central and peripheral manifestations of MS pathology. Our findings support a cell-specific regulation of EGC phenotype through SOX10 expression level and identify SOX10-regulated genes relevant to EGC function. This research advances the understanding of EGC diversity and provide information about glial cells targeting in neuroinflammatory disorders.</p>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-025-02321-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143455660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chitinase-3 Like-Protein-1 Signature in Neurological Disorders: Emphasis on Stroke","authors":"Khiany Mathias,&nbsp;Richard Simon Machado,&nbsp;Naíla Maciel Andrade,&nbsp;Natalia Piacentini,&nbsp;Carla Damasio Martins,&nbsp;Josiane Somariva Prophiro,&nbsp;Fabricia Petronilho","doi":"10.1007/s12031-025-02311-0","DOIUrl":"10.1007/s12031-025-02311-0","url":null,"abstract":"<div><p>Chitinase-3 like-protein-1 (CHI3L1) is a protein involved in various pathological conditions, including infectious, allergic, metabolic, cardiovascular, and neurological diseases. In the central nervous system, glial cells, especially activated astrocytes, are the primary sources of CHI3L1 synthesis and secretion. In neurodegenerative diseases, such as Alzheimer's disease, elevated levels of CHI3L1 are correlated with greater cognitive decline and neuroinflammation. Regarding stroke, CHI3L1 is a relevant biomarker associated with an increased risk of adverse events and mortality, particularly in patients with elevated levels following the onset of symptoms. Overall, the presence of CHI3L1 may reflect disease severity and aid in predicting outcomes. This narrative review explores the potential role of CHI3L1 in neurological diseases, with an emphasis on stroke, and it may contribute to guiding the development of effective inhibitors, which could be an attractive therapeutic approach for treating this condition.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-025-02311-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cdh23 Gene Mutation–Induced Vestibular Dysfunction in Mice: Abnormal Stereocilia Bundle and Otolith Development and Activation of p53/FoxO Signaling Pathway","authors":"Lihuan Tang,&nbsp;Yuancheng Wu,&nbsp;Kai Zhang,&nbsp;Daoli Xie,&nbsp;Xiaojing Kuang,&nbsp;Lan Wang,&nbsp;Zehua Sun,&nbsp;Ruishuang Geng,&nbsp;Juan Hu,&nbsp;Yan Sun,&nbsp;Tihua Zheng,&nbsp;Bo Li,&nbsp;Qingyin Zheng","doi":"10.1007/s12031-025-02318-7","DOIUrl":"10.1007/s12031-025-02318-7","url":null,"abstract":"<div><p>Vestibular dysfunction (VD) is increasingly acknowledged as a significant contributor to falls and deterioration in health. <i>Cadherin 23</i> (<i>Cdh23</i>) serves as an essential protein responsible for facilitating the mechanical transduction processes in hair cells, and variations in this gene have been recognized as possible factor to auditory impairments and VD. The gene <i>Cdh23</i> encodes glycoproteins that play a role in cell adhesion and are crucial for the development of stereocilia bundles. In this research, we generated CDH23 functional null mice (<i>Cdh23</i>^{<i>V2J2/V2J2</i>}). Here, our findings indicated that <i>Cdh23</i>^{<i>V2J2/V2J2</i>} mice exhibited weakened balance and coordination abilities, characterized by rotation and head nodding movements. The development of stereocilia and otoliths was abnormal in these mice. Scanning electron microscopy (SEM) analysis revealed abnormal changes in the arrangement and length of stereocilia bundles in <i>Cdh23</i>^{<i>V2J2/V2J2</i>} mice compared to wild-type mice. The abnormal alterations of otolith shape in <i>Cdh23</i>^{<i>V2J2/V2J2</i>} mice also were observed, which was smaller in saccules but larger in utricles. Furthermore, we also observed that the number of vestibular hair cells (VHCs) decreased in <i>Cdh23</i>^{<i>V2J2/V2J2</i>} mice, along with significant activation of the p53 and FoxO signaling pathways at postnatal day 56 (P56). This study elucidates potential mechanisms, histopathological features, and resultant genomic alterations associated with VD in <i>Cdh23</i>^{<i>V2J2/V2J2</i>} mice, thereby establishing a scientific foundation for prospective vestibular rehabilitative interventions.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143438613","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}