Molecular Neurobiology最新文献

{"title":"Nutritional Strategies in Major Depression Disorder: From Ketogenic Diet to Modulation of the Microbiota-Gut-Brain Axis.","authors":"Ali Nikdasti, Elaheh Sadat Khodadadi, Felora Ferdosi, Ehsan Dadgostar, Sheida Yahyazadeh, Parasta Heidari, Sajad Ehtiati, Omid Vakili, Seyyed Hossein Khatami","doi":"10.1007/s12035-024-04446-4","DOIUrl":"10.1007/s12035-024-04446-4","url":null,"abstract":"<p><p>Major depressive disorder (MDD) is a leading cause of disability worldwide. While traditional pharmacological treatments are effective for many cases, a significant proportion of patients do not achieve full remission or experience side effects. Nutritional interventions hold promise as an alternative or adjunctive approach, especially for treatment-resistant depression. This review examines the potential role of nutrition in managing MDD through addressing biological deficits and modulating pathways relevant to its pathophysiology. Specifically, it explores the ketogenic diet and gut microbiome modulation through various methods, including probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation. Numerous studies link dietary inadequacies to increased MDD risk and deficiencies in nutrients like omega-3 s, vitamins D and B, magnesium, and zinc. These deficiencies impact neurotransmitters, inflammation, and other biological factors in MDD. The gut-brain axis also regulates mood, stress response, and immunity, and disruptions are implicated in MDD. While medications aid acute symptoms, nutritional strategies may improve long-term outcomes by preventing relapse and promoting sustained remission. This comprehensive review aims to provide insights into nutrition's multifaceted relationship with MDD and its potential for developing more effective integrated treatment approaches.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"2973-2994"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080894","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":"TUBB4A Inhibits Glioma Development by Regulating ROS-PINK1/Parkin-Mitophagy Pathway.","authors":"Xueru Xi, Suqin Chen, Xiaoli Zhao, Zimu Zhou, Shanjie Zhu, Xurui Ren, Xiaomei Wang, Jing Wu, Shuai Mu, Xianwen Li, Enfang Shan, Yan Cui","doi":"10.1007/s12035-024-04459-z","DOIUrl":"10.1007/s12035-024-04459-z","url":null,"abstract":"<p><p>Glioma is a refractory malignant tumor with a powerful capacity for invasiveness and a poor prognosis. This study aims to investigate the role and mechanism of tubulin beta class IVA (TUBB4A) in glioma progression. The differential expression of TUBB4A in humans was obtained from databases and analyzed. Glioma cells U251-MG and U87-MG were intervened by pcDNA3.1(+) and TUBB4A overexpression plasmid. MTT, CCK8, LDH, wound healing, transwell, and western blotting were used to explore whether TUBB4A participates in the development of glioma. Reactive oxygen species (ROS) were detected by the DCFH-DA probe. Mitochondrial membrane potential (MMP) was examined by JC-1. It was found that TUBB4A expression level correlated with tumor grade, IDH1 status, 1p/19q status, and poor survival in glioma patients. In addition, TUBB4A overexpression inhibited the proliferation, migration, and invasion of U251-MG and U87-MG, while increasing the degree of apoptosis. Notably, TUBB4A overexpression promotes ROS generation and MMP depolarization, and induces mitophagy through the PINK1/Parkin pathway. Interestingly, mitochondria-targeted ROS scavenger reversed the effect of TUBB4A overexpression on PINK1/Parkin expression and mitophagy, whereas mitophagy inhibitor did not affect ROS production. And the effect of TUBB4A overexpression on mitophagy and glioma progression was consistent with that of PINK1/Parkin agonist. In conclusion, TUBB4A is a molecular marker for predicting the prognosis of glioma patients and an effective target for inhibiting glioma progression by regulating ROS-PINK1/Parkin-mitophagy pathway.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3125-3142"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126159","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":"Mild Blast Exposure Dysregulates Metabolic Pathways and Correlation Networking as Evident from LC-MS-Based Plasma Profiling.","authors":"Ruchi Baghel, Kiran Maan, Seema Dhariwal, Megha Kumari, Apoorva Sharma, Kailash Manda, Richa Trivedi, Poonam Rana","doi":"10.1007/s12035-024-04429-5","DOIUrl":"10.1007/s12035-024-04429-5","url":null,"abstract":"<p><p>Blast-induced trauma is emerging as a serious threat due to its wide pathophysiology where not only the brain but also a spectrum of organs is being affected. In the present study, we aim to identify the plasma-based metabolic dysregulations along with the associated temporal changes at 5-6 h, day 1 and day 7 post-injury in a preclinical animal model for blast exposure, through liquid chromatography-mass spectrometry (LC-MS). Using significantly advanced metabolomic and statistical bioinformatic platforms, we were able to elucidate better and unravel the complex networks of blast-induced neurotrauma (BINT) and its interlinked systemic effects. Significant changes were evident at 5-6 h with maximal changes at day 1. Temporal analysis also depicted progressive changes which continued till day 7. Significant associations of metabolic markers belonging to the class of amino acids, energy-related molecules, lipids, vitamin, hormone, phenolic acid, keto and histidine derivatives, nucleic acid molecules, uremic toxins, and uronic acids were observed. Also, the present study is the first of its kind where comprehensive, detailed pathway dysregulations of amino acid metabolism and biosynthesis, perturbed nucleotides, lipid peroxidation, and nucleic acid damage followed by correlation networking and multiomics networking were explored on preclinical animal models exposed to mild blast trauma. In addition, markers for systemic changes (renal dysfunction) were also observed. Global pathway predictions of unannotated peaks also presented important insights into BINT pathophysiology. Conclusively, the present study depicts important findings that might help underpin the biological mechanisms of blast-induced brain or systemic trauma.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3143-3166"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133210","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":"An In Silico Study on Withania somnifera Bioactives and Curcumin Analogs as Potential Inducers of Smoothened (Smo) Receptor of Sonic Hedgehog (SHH) Pathway to Promote Oligodendrogenesis.","authors":"Shrey Dwivedi, Shristi Modanwal, Sneha Ranjan, Ashutosh Mishra, Nidhi Mishra, Sangeeta Singh","doi":"10.1007/s12035-024-04489-7","DOIUrl":"10.1007/s12035-024-04489-7","url":null,"abstract":"<p><p>Demyelinating disorder is a subset of neurodegenerative conditions wherein factors such as aging and/or auto-immune attack cause damage and degradation of myelin sheath which enwraps the neuronal axons. Lowered axonal integrity and sub-par conduction of nerve impulses due to impaired action potentials make neurodegeneration imminent as the neurons do not have mitotic ability to replenish their numbers. Oligodendrocytes (OLs) myelinate the axonal segments of neurons and perform neuronal maintenance. Neuroregenerative stem cell therapy exploits this property for remyelination by targeting OL replenishment using in vitro stem cell differentiation protocols for inducing OL lineage cells. But some shortcomings of such protocols are over-reliance on synthetic inducers, lengthy differentiation process, low differentiation efficiency besides being financially expensive. This in silico study sought to identify herbal substitutes of currently available OL-lineage-specific synthetic inducers from a virtual library of curcumin analogs and Withania somnifera bioactives. Smoothened (Smo) receptor belonging to the canonical sonic hedgehog (SHH) signaling pathway promotes in vivo differentiation of OLs as well as their subsequent lineage progression to myelinating OLs. Therefore, we performed pharmacokinetics prediction for the bioactives followed by their molecular docking and molecular dynamics simulation with Smo. From a pool of 1289 curcumin analogs and 80 Withania somnifera-derived bioactives, the best docked ligands were identified as the compounds with PubChem IDs 68815167 and 25880, respectively. Molecular dynamics simulation of these ligands further concluded the Withania somnifera bioactive 25880 to have the best activity with Smo. This compound may be deemed as a potential lead molecule for an agonistic interaction with and activation of Smo to initialize its downstream signaling cascade for enriching OL differentiation.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3523-3543"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291485","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":"The Effects of Ionotropic GABA Receptor Blockage on the Brain in Rats with Induced Sepsis.","authors":"Gulten Ates, Elif Ozkok, Gul Ipek Gundogan, Sule Tamer","doi":"10.1007/s12035-024-04505-w","DOIUrl":"10.1007/s12035-024-04505-w","url":null,"abstract":"<p><p>Encephalopathy following sepsis is defined as life-threatening organ failure due to the irregular response of the host to infection and has high mortality and morbidity rates. The present study aimed to investigate the effects of inflammation and the gamma-aminobutyric acid-A (GABA_A) receptor antagonist, bicuculline, on brain tissue in rats with sepsis. Sepsis was experimentally generated using lipopolysaccharide (LPS). The rats were divided into four groups: control, LPS (10 mg/kg i.p.), bicuculline (1.5 mg/kg s.c.), and LPS+Bic. Electrophysiologic recordings and body temperature measurements were completed at the 24th hour, and samples were taken. TNF-α, IL-10, GABA, and MDA levels were measured. Tissue imaging was performed using S100-ß, NEUN, and synaptophysin antibodies. One-way ANOVA followed by the Tukey test was performed for statistical analysis. Inflammatory parameters significantly increased in brain tissue in the LPS group compared with the other groups (TNF-α, [F (3.14) = 6.015, p = 0.042]; IL-10, [F (3.15) = 9.013, p = 0.02]). Tissue imaging results were as follows: S100-ß involvement increased, and NeuN and synaptophysin involvement decreased in the LPS group [F (3.21) = 18.016, p = 0.006, for S100-ß; F (3.21) = 19.071, p = 0.003, for NeuN; F (3.21) = 18.098, p = 0.005, for synaptophysin]. In electrophysiologic recordings, we observed activity consistent with acute non-focal seizures in the LPS group. Contrarily, the control and other comparison groups exhibited normal resting neural activity. Bicuculline may be used as a therapeutic agent in sepsis to maintain the neurotransmitter and pro- and anti-inflammatory cytokine balance and reduce lipid peroxidation with its effects of acetylcholine esterase inhibition and GABA_A receptor antagonism.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3544-3555"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291494","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":"Role of Exercise on Neuropathic Pain in Preclinical Models: Perspectives for Neuroglia.","authors":"Chen-Chen Zhu, Yi-Li Zheng, Chan Gong, Bing-Lin Chen, Jia-Bao Guo","doi":"10.1007/s12035-024-04511-y","DOIUrl":"10.1007/s12035-024-04511-y","url":null,"abstract":"<p><p>The benefits of exercise on neuropathic pain (NP) have been demonstrated in numerous studies. In recent studies, inflammation, neurotrophins, neurotransmitters, and endogenous opioids are considered as the main mechanisms. However, the role of exercise in alleviating NP remains unclear. Neuroglia, widely distributed in both the central and peripheral nervous systems, perform functions such as support, repair, immune response, and maintenance of normal neuronal activity. A large number of studies have shown that neuroglia play an important role in the occurrence and development of NP, and exercise can alleviate NP by regulating neuroglia. This article reviewed the involvement of neuroglia in the development of NP and their role in the exercise treatment of NP, intending to provide a theoretical basis for the exercise treatment strategy of NP.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3684-3696"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308082","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":"Single-Nucleus Landscape of Glial Cells and Neurons in Alzheimer's Disease.","authors":"Mengru Lu, Jiaxin Li, Qi Huang, Daniel Mao, Grace Yang, Yating Lan, Jingyi Zeng, Mika Pan, Shengliang Shi, Donghua Zou","doi":"10.1007/s12035-024-04428-6","DOIUrl":"10.1007/s12035-024-04428-6","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disease with a projected significant increase in incidence. Therefore, this study analyzed single-nucleus AD data to provide a theoretical basis for the clinical development and treatment of AD. We downloaded AD-related monocyte data from the Gene Expression Omnibus database, annotated cells, compared cell abundance between groups, and investigated glial and neuronal cell biological processes and pathways through functional enrichment analysis. Furthermore, we constructed a global regulatory network for AD based on cell communication and ecological analyses. Our findings revealed increased abundance of Capping Protein Regulator And Myosin 1 linker 1 (CARMIL1)⁺ astrocytes (AST), Immunoglobulin Superfamily Member 21 (IGSF21)⁺ microglia (MIC), SRY-Box Transcription Factor 6 (SOX6)⁺ inhibitory neurons (InNeu), and laminin alpha-2 chain (LAMA2)⁺ oligodendrocytes (OLI) cell subgroups in tissues of patients with AD, while prostaglandin D2 synthase (PTGDS)⁺ AST, Src Family Tyrosine Kinase (FYN)⁺ MIC, and Proteolipid Protein 1 (PLP1)⁺ InNeu subgroups specifically decreased. We found that the cell phenotype of patients with AD shifted from a simpler to a more complex state compared to the control group. Cell communication analysis revealed strong communication between MIC and NEU. Furthermore, AST, MIC, NEU, and OLI were involved in oxidative stress- and inflammation-related pathways, potentially contributing to disease development. This study provides a theoretical basis for further exploring the specific mechanisms underlying AD.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"2695-2709"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996145","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":"SRF Facilitates Transcriptional Inhibition of Gem Expression by m6A Methyltransferase METTL3 to Suppress Neuronal Damage in Epilepsy.","authors":"Lianling Li, Zhiguo Liu","doi":"10.1007/s12035-024-04396-x","DOIUrl":"10.1007/s12035-024-04396-x","url":null,"abstract":"&lt;p&gt;&lt;p&gt;A bioinformatics analysis was conducted to screen for relevant expression datasets of the transcription factor SRF knockout mice. The aim was to investigate the relationship between SRF and m6A-related genes, predict how SRF regulates the m6A modification of GEM genes mediated by METTL3, and explore potential molecular mechanisms associated with neurotrauma. Disease gene databases such as GeneCards, DisGeNET, and Phenolyzer, and transcription factor databases TFDB and TRRUST, were used to obtain epilepsy-related genes and transcription factors. The intersection was then selected. Expression data of SRF knockout epilepsy mice were obtained from the GEO database and used to filter differentially expressed genes. Important module genes related to the disease were selected through WGCNA co-expression analysis. The intersection between these genes and the differentially expressed genes was performed, followed by PPI network analysis and GO/KEGG enrichment analysis. Furthermore, the core genes were selected using the cytoHubba plugin of the Cytoscape software. Differential expression analysis was performed on m6A-related factors in the GEO dataset, and the relationship between SRF and m6A-related factors and core genes was analyzed. The m6A binding sites of SRF with the METTL3 promoter and target gene Gem were predicted using the AnimalTFDB and SRAMP websites, respectively. We found that the transcription factor SRF may be a key gene in epilepsy during neuronal development. Further WGCNA analysis showed that 129 module genes were associated with SRF knockout epilepsy, and these differentially expressed genes were mainly enriched in the neuroactive ligand-receptor interaction pathway. The final results indicate that knocking out SRF may inhibit the transcription of METTL3, thereby inhibiting the m6A modification of Gem and leading to upregulation of Gem expression, thereby playing an important role in neuronal damage. Knocking out the SRF gene may inhibit the transcription of m6A methyltransferase METTL3, thereby inhibiting the m6A modification of GEM genes mediated by METTL3, promoting GEM gene expression, and leading to the occurrence of epilepsy-related neuron injury. Further investigation revealed that SRF overexpression can potentially enhance the transcription of METTL3, thus promoting m6A modification of GEM, resulting in downregulation of GEM expression. This process regulates oxidative stress in epileptic mouse neurons, suppresses inflammatory responses, and mitigates associated damage. Additionally, an in vitro neuronal epileptic model was established, and experimental techniques such as qRT-PCR and WB were employed to assess the expression of SRF, METTL3, and GEM in hippocampal tissues and neurons. The experimental results were consistent with our predictions, demonstrating that overexpression of SRF can inhibit the development of epilepsy-related neuronal damage. This study reveals that knockout of the SRF gene may suppress the transcr","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"2903-2925"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073317","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":"Curcumin Alleviates Microglia-Mediated Neuroinflammation and Neuronal Ferroptosis Following Experimental Subarachnoid Hemorrhage by Modulating the Nrf2/HO-1 Signaling Pathway.","authors":"Yao Xu, Yongsheng Liu, Yan Wu, Jingshan Sun, Xiaocheng Lu, Kun Dai, Yiting Zhang, Chengliang Luo, Jian Zhang","doi":"10.1007/s12035-024-04443-7","DOIUrl":"10.1007/s12035-024-04443-7","url":null,"abstract":"<p><p>Early brain injury caused by subarachnoid hemorrhage (SAH) is associated with inflammatory response and ferroptosis. Curcumin alleviates neuroinflammation and oxidative stress by as yet unknown neuroprotective mechanisms. The objective of this study was to investigate the impact of curcumin on neuronal ferroptosis and microglia-induced neuroinflammation following SAH. By examining Nrf2/HO-1 expression levels and ferroptosis biomarkers expression both in vitro and in vivo, it was demonstrated that curcumin effectively suppressed ferroptosis in neurons after SAH through modulation of the Nrf2/HO-1 signaling pathway. Furthermore, by analyzing the expression levels of Nrf2, HO-1, p-p65, and inflammation-related genes, it was confirmed that curcumin could prevent the upregulation of pro-inflammatory factors following SAH by regulating the Nrf2/HO-1/NF-κB signaling pathway in microglia. The ability of curcumin to reduce neuronal damage and cerebral edemas after SAH in mice was validated using TUNEL staining, Nissl staining, and measurement of brain tissue water content. Additionally, through implementation of the modified Garcia test, open field test, and Y-maze test, it was established that curcumin ameliorated neurobehavioral impairments in mice post-SAH. Taken together, these data suggest that curcumin may offer a promising therapeutic approach for improving outcomes following SAH by concurrently attenuating neuronal ferroptosis and reducing neuroinflammation.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"2995-3010"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109586","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":"Activation of P2X7R Inhibits Proliferation and Promotes the Migration and Differentiation of Schwann Cells.","authors":"Wenfeng Su, Xiaowen He, Zhihao Lin, Jinghui Xu, Jianghong Shangguan, Zhongya Wei, Yayu Zhao, Lingyan Xing, Yun Gu, Gang Chen","doi":"10.1007/s12035-024-04460-6","DOIUrl":"10.1007/s12035-024-04460-6","url":null,"abstract":"<p><p>In the vertebrate nervous system, myelination of nerve fibers is crucial for the rapid propagation of action potentials through saltatory conduction. Schwann cells-the main glial cells and myelinating cells of the peripheral nervous system-play a crucial role in myelination. Following injury during the repair of peripheral nerve injuries, a significant amount of ATP is secreted. This ATP release acts to trigger the dedifferentiation of myelinating Schwann cells into repair cells, an essential step for axon regeneration. Subsequently, to restore nerve function, these repair cells undergo redifferentiate into myelinating Schwann cells. Except for P2X4R, purine receptors such as P2X7R also play a significant role in this process. In the current study, decreased expression of P2X7R was observed after sciatic nerve injury, followed by a gradual increase to the normal level of P2X7R expression. In vivo experiments showed that the activation of P2X7R using an agonist injection promoted remyelination, while the antagonists hindered remyelination. Further, in vitro experiments supported these findings and demonstrated that P2X7R activation inhibited the proliferation of Schwann cells, but it promoted the migration and differentiation of the Schwann cells. Remyelination is a prominent feature of the nerve regeneration. In the current study, it was proposed that the manipulation of P2X7R expression in Schwann cells after nerve injury could be effective in facilitating nerve remyelination.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3067-3081"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120227","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}