Frontiers in Molecular Neuroscience最新文献

{"title":"Neurotherapeutic impact of vanillic acid and ibudilast on the cuprizone model of multiple sclerosis.","authors":"Rasha M Alderbi, Mohammad Z Alam, Badrah S Alghamdi, Hadeil M Alsufiani, Gamal S Abd El-Aziz, Ulfat M Omar, Maryam A Al-Ghamdi","doi":"10.3389/fnmol.2024.1503396","DOIUrl":"10.3389/fnmol.2024.1503396","url":null,"abstract":"<p><p>Multiple sclerosis (MS) affects 2.8 million people worldwide. Although the cause is unknown, various risk factors might be involved. MS involves the immune system attacking the central nervous system's myelin sheath, leading to neuron damage. This study used a cuprizone (CPZ)-intoxicated mouse model to simulate MS's demyelination/remyelination process. It evaluated the molecular, histological, and behavioral effects of vanillic acid (VA), a natural phenolic acid, alone and with Ibudilast (IBD), a clinically tested MS medication. Mice were divided into a control group (regular chow) and a CPZ group (0.3% cuprizone chow for 5 consecutive weeks). During remyelination, the CPZ group was split into four groups: no therapy, 10 mg/kg of IBD, 30 mg/kg of VA, and combined, each treated for 4 weeks. Behavioral, biochemical, molecular, and histopathological tests occurred in the 5^th week (demyelination), 7^th (early remyelination), and 9^th (late remyelination). Cognitive assessments were at weeks 5 and 9. VA enhanced motor, coordination, and cognitive impairments in CPZ-intoxicated mice and improved histopathological, molecular, and biochemical features during early remyelination. IBD improved behavioral abnormalities across all tests, but combined therapy showed no significant difference from single therapies. Further investigations are necessary to understand VA's mechanisms and potential as an MS treatment.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1503396"},"PeriodicalIF":3.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum metabolomic signatures of patients with rare neurogenetic diseases: an insight into potential biomarkers and treatment targets.","authors":"Nalaka Wijekoon, Lakmal Gonawala, Pyara Ratnayake, Darshana Sirisena, Harsha Gunasekara, Athula Dissanayake, Dhammika Amaratunga, Harry W M Steinbusch, Yetrib Hathout, Eric P Hoffman, Ashwin Dalal, Chandra Mohan, K Ranil D de Silva","doi":"10.3389/fnmol.2024.1482999","DOIUrl":"10.3389/fnmol.2024.1482999","url":null,"abstract":"<p><strong>Introduction: </strong>To further advance our understanding of Muscular Dystrophies (MDs) and Spinocerebellar Ataxias (SCAs), it is necessary to identify the biological patterns associated with disease pathology. Although progress has been made in the fields of genetics and transcriptomics, there is a need for proteomics and metabolomics studies. The present study aimed to be the first to document serum metabolic signatures of MDs (DMD, BMD, and LGMD 2A) SCAs (SCA 1-3), from a South Asian perspective.</p><p><strong>Methods: </strong>A total of 28 patients (SCA 1-10, SCA 2-2, SCA 3-2, DMD-10, BMD-2, LGMD-2) and eight controls (aged 8-65 years) were included. Metabolomic analysis was performed by Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS), with support from the Houston Omics Collaborative.</p><p><strong>Results and discussion: </strong>Amino acid metabolism was the primary altered super pathway in DMD followed by carbohydrate metabolism and lipid metabolism. In contrast, BMD and LGMD 2A exhibited a more prominent alteration in lipid metabolism followed by amino acid metabolism. In SCAs, primarily lipid, amino acid, peptide, nucleotide, and xenobiotics pathways are affected. Our findings offer new insights into the variance of metabolite levels in MD and SCA, with substantial implications for pathology, drug development, therapeutic targets and clinical management. Intriguingly, this study identified two novel metabolites associated with SCA. This pilot cross-sectional study warrants further research involving larger groups of participants, to validate our findings.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1482999"},"PeriodicalIF":3.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insight into interplay between PANoptosis and autophagy: novel therapeutics in ischemic stroke.","authors":"He-Yan Tian, Yun-Xing Lei, Jing-Tao Zhou, Long-Jun Liu, Tong Yang, Yue Zhou, Jin-Wen Ge, Chen Xu, Zhi-Gang Mei","doi":"10.3389/fnmol.2024.1482015","DOIUrl":"10.3389/fnmol.2024.1482015","url":null,"abstract":"<p><p>PANoptosis is a novelly defined mode of programmed cell death that involves the activation of multiple cellular death pathways, including pyroptosis, apoptosis, and necroptosis, triggering robust inflammatory reactions. Autophagy is a crucial cellular process that maintains cellular homeostasis and protects cells from various stresses. PANoptosis and autophagy, both vital players in the intricate pathological progression of ischemic stroke (IS), a brain ailment governed by intricate cell death cascades, have garnered attention in recent years for their potential interplay. While mounting evidence hints at a crosstalk between these two processes in IS, the underlying mechanisms remain elusive. Therefore, this review delves into and dissects the intricate mechanisms that underpin the intersection of PANoptosis and autophagy in this devastating condition. In conclusion, the crosstalk between PANoptosis and autophagy in IS presents a promising target for the development of novel stroke therapies. Understanding the interplay between these two pathways offers a much-needed insight into the underlying mechanisms of IS and opens the possibility for new therapeutic strategies.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1482015"},"PeriodicalIF":3.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urine miRNA signature as potential non-invasive diagnostic biomarker for Hirschsprung's disease.","authors":"Abhijit Sreepada, Rasul Khasanov, Enas Zoheer Elkrewi, Carolina de la Torre, Judith Felcht, Ahmad A Al Abdulqader, Richard Martel, Nicolás Andrés Hoyos-Celis, Michael Boettcher, Lucas M Wessel, Karl-Herbert Schäfer, María Ángeles Tapia-Laliena","doi":"10.3389/fnmol.2024.1504424","DOIUrl":"10.3389/fnmol.2024.1504424","url":null,"abstract":"<p><p>Hirschsprung's disease (HSCR) is characterized by congenital absence of ganglion cells in the gastrointestinal tract, which leads to impaired defecation, constipation and intestinal obstruction. The current diagnosis of HSCR is based on Rectal Suction Biopsies (RSBs), which could be complex in newborns. Occasionally, there is a delay in diagnosis that can increase the risk of clinical complications. Consequently, there is room for new non-invasive diagnostic methods that are objective, more logistically feasible and also deliver a far earlier base for a potential surgical intervention. In recent years, microRNA (miRNA) has come into the focus as a relevant early marker that could provide more insights into the etiology and progression of diseases. Therefore, in the search of a non-invasive HSCR biomarker, we analyzed miRNA expression in urine samples of HSCR patients. Results from 5 HSCR patients using microarrays, revealed hsa-miR-378 h, hsa-miR-210-5p, hsa-miR-6876-3p, hsa-miR-634 and hsa-miR-6883-3p as the most upregulated miRNAs; while hsa-miR-4443, hsa-miR-22-3p, hsa-miR-4732-5p, hsa-miR-3187-5p, and hsa-miR-371b-5p where the most downregulated miRNAs. Further search in miRNAwalk and miRDB databases showed that certainly most of these dysregulated miRNAs identified target HSCR associated genes, such as <i>RET, GDNF, BDNF, EDN3, EDNRB, ERBB, NRG1, SOX10;</i> and other genes implied in neuronal migration and neurogenesis. Finally, we could also validate some of these miRNA changes in HSCR urine by RT-qPCR. Altogether, our analyzed HSCR cohort presents a dysregulated miRNA expression presents that can be detected in urine. Our findings open the possibility of using specific urine miRNA signatures as non-invasive HSCR diagnosis method in the future.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1504424"},"PeriodicalIF":3.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and molecular mechanisms of hydrocephalus.","authors":"Xuehai Deng, Yiqian Chen, Qiyue Duan, Jianlin Ding, Zhong Wang, Junchi Wang, Xinlong Chen, Liangxue Zhou, Long Zhao","doi":"10.3389/fnmol.2024.1512455","DOIUrl":"10.3389/fnmol.2024.1512455","url":null,"abstract":"<p><p>Hydrocephalus is a neurological condition caused by aberrant circulation and/or obstructed cerebrospinal fluid (CSF) flow after cerebral ventricle abnormal dilatation. In the past 50 years, the diagnosis and treatment of hydrocephalus have remained understudied and underreported, and little progress has been made with respect to prevention or treatment. Further research on the pathogenesis of hydrocephalus is essential for developing new diagnostic, preventive, and therapeutic strategies. Various genetic and molecular abnormalities contribute to the mechanisms of hydrocephalus, including gene deletions or mutations, the activation of cellular inflammatory signaling pathways, alterations in water channel proteins, and disruptions in iron metabolism. Several studies have demonstrated that modulating the expression of key proteins, including TGF-β, VEGF, Wnt, AQP, NF-κB, and NKCC, can significantly influence the onset and progression of hydrocephalus. This review summarizes and discusses key mechanisms that may be involved in the pathogenesis of hydrocephalus at both the genetic and molecular levels. While obstructive hydrocephalus can often be addressed by removing the obstruction, most cases require treatment strategies that involve merely slowing disease progression by correcting CSF circulation patterns. There have been few new research breakthroughs in the prevention and treatment of hydrocephalus.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1512455"},"PeriodicalIF":3.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11746911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling of auditory neuropathy spectrum disorders associated with the <i>TEME43</i> variant reveals impaired gap junction function of iPSC-derived glia-like support cells.","authors":"Xiaoming Kang, Lu Ma, Jie Wen, Wei Gong, Xianlin Liu, Yihan Hu, Zhili Feng, Qiancheng Jing, Yuexiang Cai, Sijun Li, Xinzhang Cai, Kai Yuan, Yong Feng","doi":"10.3389/fnmol.2024.1457874","DOIUrl":"10.3389/fnmol.2024.1457874","url":null,"abstract":"<p><p>Auditory neuropathy spectrum disorder (ANSD) is an auditory dysfunction disorder characterized by impaired speech comprehension. Its etiology is complex and can be broadly categorized into genetic and non-genetic factors. <i>TMEM43</i> mutation is identified as a causative factor in ANSD. While some studies have been conducted using animal models, its pathogenic mechanisms in humans remain unclear. TMEM43 is predominantly expressed in cochlear glia-like support cells (GLSs) and plays a vital role in gap junction intercellular communication. In this work, we utilized induced pluripotent stem cells from an ANSD patient carrying the <i>TMEM43</i> gene mutation c.1114C>T (p.Arg372Ter) and directed their differentiation toward GLSs to investigate the effect of <i>TMEM43</i> mutation on the function of gap junctions in cochlear GLSs <i>in vitro</i>. Reduced expression of genes associated with GLSs characteristics and reduced gap junction intercellular communication in <i>TMEM43</i> mutant cell lines were observed compared to controls. Transcriptome analysis revealed that differentially expressed genes were significantly enriched in pathways related to cell proliferation, differentiation, extracellular space and adhesion. Furthermore, significant alterations were noted in the PI3K-Akt signaling pathway and the calcium signaling pathway, which could potentially influence gap junction function and contribute to hearing loss. In summary, our study based on patient-derived iPSCs sheds new light on the molecular mechanisms by which <i>TMEM43</i> mutations may lead to ANSD. These mutations could result in developmental defects in GLSs and a diminished capacity for gap junction function, which may be implicated in the auditory deficits observed in ANSD patients. Our study explored the pathological effects of the <i>TMEM43</i> mutation and its causal relationship with ANSD using a patient-derived iPSC-based GLSs model, providing a foundation for future mechanistic studies and potential drug screening efforts.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1457874"},"PeriodicalIF":3.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping the research landscape of microRNAs in pain: a comprehensive bibliometric analysis.","authors":"Huaiming Wang, Qin Li, Jiang Zou, Jinjun Shu, Aimin Zhang, Hongwei Zhang, Qi Zhao, Shunxin Liu, Chan Chen, Guo Chen","doi":"10.3389/fnmol.2024.1493822","DOIUrl":"https://doi.org/10.3389/fnmol.2024.1493822","url":null,"abstract":"<p><strong>Background and objectives: </strong>MicroRNAs (miRNAs) have demonstrated significant potential in pain medicine research, including mechanisms, diagnosis, and therapy. However, no relative bibliometric analysis has been performed to summarize the progress in this area quantitatively.</p><p><strong>Methods: </strong>Literature was retrieved from the Web of Science Core Collection online database. A total of 1,295 papers were retrieved between January 1, 2000 and September 21, 2023 and underwent visualization and analysis using R software [Library [bibliometrix] and biblioshiny packages], VOSviewer (version 1.6.18), CiteSpace software (version 6.2.R4), and the bibliometrics website (http://bibliometric.com).</p><p><strong>Results: </strong>Publications in this field have increased annually since 2000, demonstrating growing research interest. China emerged as the most productive country, followed by the United States and Germany. Keyword analysis identified \"expression,\" \"neuropathic pain,\" and \"microRNAs\" as the most relevant keywords. Extensive collaboration among countries and institutions was also observed.</p><p><strong>Conclusion: </strong>The bibliometric analysis revealed a rapid growth of publications related to miRNAs and pain in the past 2 decades. Keywords analysis indicates that \"expression,\" \"neuropathic pain,\" and \"microRNA\" are the most frequently used words in this research field. However, more robust and globally recognized basic studies and clinical trials from prestigious journals are required.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1493822"},"PeriodicalIF":3.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of Aha1 in cancer and neurodegeneration.","authors":"Brian S J Blagg, Kevin C Catalfano","doi":"10.3389/fnmol.2024.1509280","DOIUrl":"https://doi.org/10.3389/fnmol.2024.1509280","url":null,"abstract":"<p><p>The 90 kDa Heat shock protein (Hsp90) is a family of ubiquitously expressed molecular chaperones responsible for the stabilization and maturation of >400 client proteins. Hsp90 exhibits dramatic conformational changes to accomplish this, which are regulated by partner proteins termed co-chaperones. One of these co-chaperones is called the activator or Hsp90 ATPase activity homolog 1 (Aha1) and is the most potent accelerator of Hsp90 ATPase activity. In conditions where Aha1 levels are dysregulated including cystic fibrosis, cancer and neurodegeneration, Hsp90 mediated client maturation is disrupted. Accumulating evidence has demonstrated that many disease states exhibit large hetero-protein complexes with Hsp90 as the center. Many of these include Aha1, where increased Aha1 levels drive disease states forward. One strategy to block these effects is to design small molecule disruptors of the Hsp90/Aha1 complex. Studies have demonstrated that current Hsp90/Aha1 small molecule disruptors are effective in both models for cancer and neurodegeration.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1509280"},"PeriodicalIF":3.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the pathogenicity and pathological characteristics of <i>NOTCH3</i> gene-sparing cysteine mutations <i>in vitro</i> and <i>in vivo</i> models.","authors":"Zhenping Gong, Wan Wang, Ying Zhao, Yadan Wang, Ruihua Sun, Haohan Zhang, Fengyu Wang, Yaru Lu, Jiewen Zhang","doi":"10.3389/fnmol.2024.1391040","DOIUrl":"https://doi.org/10.3389/fnmol.2024.1391040","url":null,"abstract":"<p><strong>Background: </strong>Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of the most common inherited cerebral small vessel diseases caused by the NOTCH3 gene mutation. This mutation leads to the accumulation of NOTCH3 extracellular domain protein (NOTCH3^ECD) into the cerebral arterioles, causing recurrent stroke, white matter lesions, and cognitive impairment. With the development of gene sequencing technology, cysteine-sparing mutations can also cause CADASIL disease, however, the pathogenicity and pathogenic mechanisms of cysteine-sparing mutations remain controversial.</p><p><strong>Objective: </strong>To analyze the pathogenicity and pathological features of cysteine-sparing mutations in both <i>in vitro</i> and <i>in vivo</i> mouse models.</p><p><strong>Methods: </strong>A cysteine-sparing mutant of NOTCH3^ECD R75Q was constructed by lentiviral transfection <i>in vitro</i>, and the <i>NOTCH3 R75Q</i> knock-in mouse model was constructed by CRISPR/Cas-mediated genome engineering <i>in vivo</i>. A cycloheximide pulse-chase experiment was used to analyze the degradation of NOTCH3 extracellular domain proteins, and the deposition characteristics of NOTCH3^ECD were quantitatively analyzed by immunohistochemical staining. The characteristics of the smooth muscle cells and granular osmiophilic materials were observed using electron microscopy.</p><p><strong>Results: </strong>We elucidated that the <i>NOTCH3 R75Q</i> mutation is pathogenic. NOTCH3^ECD R75Q was found to be resistant to protein degradation and more likely to cause abnormal aggregation of NOTCH3^ECD, resulting in reduced cell activity <i>in vitro</i>. The <i>NOTCH3 R75Q</i> mouse model showed pathological characteristics of CADASIL, with age-dependent NOTCH3^ECD, granular osmiophilic material, and degenerated smooth muscle cells detected in the brain.</p><p><strong>Conclusion: </strong>To our knowledge, this is the first study to analyze the pathogenicity of <i>NOTCH3 R75Q</i> cysteine-sparing mutations in both <i>in vitro</i> and <i>in vivo</i> models. We demonstrate that NOTCH3^ECD induced by <i>NOTCH3 R75Q</i> mutation has toxic effects on cells and reveal the deposition characteristics of NOTCH3^ECD in the brain. This provides a feasible model and lays the foundation for further studies on the pathogenesis and therapeutic strategies of <i>NOTCH3</i> cysteine-sparing mutations.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1391040"},"PeriodicalIF":3.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of mechanoreceptor Piezo1 inhibits enteric neuronal growth and migration <i>in vitro</i>.","authors":"Chioma Moneme, Oluyinka O Olutoye, Michał F Sobstel, Yuwen Zhang, Xinyu Zhou, Jacob L Kaminer, Britney A Hsu, Chengli Shen, Arabinda Mandal, Hui Li, Ling Yu, Swathi Balaji, Sundeep G Keswani, Lily S Cheng","doi":"10.3389/fnmol.2024.1474025","DOIUrl":"10.3389/fnmol.2024.1474025","url":null,"abstract":"<p><strong>Introduction: </strong>Dysfunction of the enteric nervous system (ENS) is linked to a myriad of gastrointestinal (GI) disorders. Piezo1 is a mechanosensitive ion channel found throughout the GI tract, but its role in the ENS is largely unknown. We hypothesize that Piezo1 plays an important role in the growth and development of the ENS.</p><p><strong>Methods: </strong>Enteric neural crest-derived progenitor cells (ENPC) were isolated from adult mouse intestine and propagated in culture as neurospheres. ENPC-derived neurons were then subject to <i>in vitro</i> stretch in the presence or absence of Piezo1 antagonist (GsMTx4). Transcriptomes of stretched and unstretched ENPC-derived cells were compared using bulk RNA sequencing. Enteric neurons were also cultured under static conditions in the presence of Piezo1 agonist (Yoda1) or antagonist. Neuronal phenotype, migration, and recovery from injury were compared between groups.</p><p><strong>Results: </strong>Though stretch did not cause upregulation of Piezo1 expression in enteric neurons, both stretch and Piezo1 activation produced similar alterations in neuronal morphology. Compared to control, neurite length was significantly shorter when stretched and in the presence of Piezo1 activation. Piezo1 inhibition prevented a significant reduction in neurite length in stretched neurons. Piezo1 inhibition also led to significantly increased neuronal migration, whereas Piezo1 activation resulted in significantly decreased neuronal migration and slower neuronal recovery from injury.</p><p><strong>Conclusion: </strong>Mechanotransduction plays an important role in regulating normal GI function. Our results suggest that the Piezo1 mechanoreceptor may play an important role in the ENS as its activation leads to decreased neuronal growth and migration. Piezo1 could be an important target for diseases of ENS dysfunction and development.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1474025"},"PeriodicalIF":3.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}