Cellular and Molecular Neurobiology最新文献

{"title":"Cycloastragenol Protects Against Cisplatin-Induced Cochlear Hair Cell Apoptosis via the PI3K/Akt/mTOR Pathway.","authors":"Tan Wang, Zhemeng Chen, Daquan Wu, Zhengjie Zhu, Kanglun Jiang, Li Gao, Tianyu Gong, Jingrong Lv, Xinsheng Huang","doi":"10.1007/s10571-026-01737-3","DOIUrl":"https://doi.org/10.1007/s10571-026-01737-3","url":null,"abstract":"<p><strong>Conclusion: </strong>Cycloastragenol protects cochlear hair cells against cisplatin-induced ototoxicity by preserving mitochondrial function, suppressing apoptosis, and activating the PI3K/Akt/mTOR signaling pathway. These findings highlight the potential of CAG as a therapeutic candidate for preventing cisplatin-induced hearing loss.</p><p><strong>Results: </strong>CAG significantly improved cell viability and reduced cisplatin-induced apoptosis in cochlear hair cells, as demonstrated by decreased TUNEL positivity, reduced apoptotic rates, and modulation of apoptosis-related proteins. CAG also preserved hair-cell marker expression and maintained cochlear hair-cell morphology. Furthermore, CAG restored mitochondrial function by increasing ATP production, maintaining ΔΨm, reducing ROS accumulation, and enhancing respiratory chain complex activities, while preventing mitochondrial fragmentation. In vivo, CAG markedly attenuated cisplatin-induced hearing loss, as indicated by improved ABR thresholds. Mechanistically, CAG activated the PI3K/Akt/mTOR signaling pathway, and inhibition of this pathway abolished its protective effects.</p><p><strong>Background: </strong>Cisplatin-induced ototoxicity, a major adverse effect of chemotherapy, results in irreversible sensorineural hearing loss primarily due to apoptotic loss of cochlear sensory hair cells. Cycloastragenol (CAG), a naturally occurring triterpenoid saponin derived from Astragalus, possesses antioxidant and anti-apoptotic properties. However, its potential protective effects against cisplatin-induced cochlear injury and the underlying mechanisms remain unclear.</p><p><strong>Methods: </strong>HEI-OC1 cells, cochlear explant cultures (including the ex vivo cochlear explant model), and a mouse model were used to evaluate the protective effects of CAG against cisplatin-induced ototoxicity. Cell viability was assessed using the CCK-8 assay, while apoptosis was evaluated by TUNEL staining, flow cytometry, and Western blotting of apoptosis-related proteins. Hair-cell markers (Myo7a and Prestin) and cochlear hair-cell morphology were examined by immunofluorescence staining. Mitochondrial function was assessed by measuring ATP levels, mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS), and respiratory chain complex activities, along with mitochondrial morphology analysis using immunofluorescence and transmission electron microscopy. Auditory function in mice was evaluated by auditory brainstem response (ABR) measurements. The involvement of the PI3K/Akt/mTOR pathway was analyzed by Western blotting and inhibition assays using the PI3K inhibitor LY294002.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834189","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":"Spinal Cord Stimulation Alleviates Neuropathic Pain Involves Regulation of the Ca²⁺/CaN/NFAT4 Pathway in Spinal Dorsal Horn Astrocytes.","authors":"Xiangmiao Li, Zhen Wu, Rongrong Wang, Jinzhu Bai","doi":"10.1007/s10571-026-01739-1","DOIUrl":"https://doi.org/10.1007/s10571-026-01739-1","url":null,"abstract":"<p><p>Spinal cord stimulation (SCS) represents an established neuromodulatory intervention for refractory neuropathic pain (NP), yet the cellular mechanisms underlying its anti-inflammatory effects remain incompletely defined. The activation of astrocytes, especially polarization into the A1-like phenotype, is crucial for the persistence of central sensitization. This study aimed to investigate whether the analgesic effects of SCS are associated with modulation of astrocyte activation and calcium ions (Ca²⁺) / calcineurin (CaN) / nuclear factors of activated T cells 4 (NFAT4) pathway signaling in the spinal dorsal horn. In a rat model of chronic constriction injury (CCI), the present study found that SCS significantly ameliorated mechanical allodynia and reduced spinal levels of proinflammatory cytokines. Furthermore, SCS suppressed spinal dorsal horn astrocyte activation and attenuated their polarization toward the A1-like phenotype. In association with these changes, SCS reduced CCI-induced spinal Ca²⁺ elevation, downregulated CaN and NFAT4 expression, and decreased NFAT4 nuclear translocation. In vitro experiments further demonstrated that inhibition of CaN or NFAT4 similarly attenuated astrocyte activation, A1-like polarization, and proinflammatory cytokine release. The findings suggest that the analgesic effect of SCS in NP is associated with suppression of Ca²⁺/CaN/NFAT4 pathway signaling and attenuation of neurotoxic A1-like astrocyte polarization and neuroinflammation. This study supports the involvement of an astrocyte-related Ca²⁺/CaN/NFAT4 signaling axis in the biological effects of SCS and provides a potential therapeutic target for improving neuromodulation-based pain management. Graphical Abstract. Spinal cord stimulation alleviates neuropathic pain and is associated with reduced Ca²⁺/CaN/NFAT4 pathway signaling, astrocyte activation, and A1-like polarization in the spinal dorsal horn. Spinal cord stimulation reverses the activation of the Ca²⁺/CaN/NFAT4 signaling pathway in spinal dorsal horn caused by peripheral nerve injury, thereby inhibiting NFAT4 nuclear translocation. This suppresses A1-like astrocyte polarization and proinflammatory cytokine release, alleviating neuropathic pain.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834200","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":"Optogenetic Strategies for Motor Recovery After Ischemic Stroke: Mechanisms and Therapeutic Implications.","authors":"Ping-Xuan Shen, Pei Wang, Hong-Xing Wang","doi":"10.1007/s10571-026-01740-8","DOIUrl":"https://doi.org/10.1007/s10571-026-01740-8","url":null,"abstract":"<p><p>Ischemic stroke frequently results in persistent motor impairment, which highlights the need for effective strategies for neural repair. Functional recovery relies fundamentally on neurobehavioral remodeling, yet traditional physical and electrical stimulation therapies often lack the necessary cell-type and spatial specificity. Optogenetics overcomes these limitations by enabling the selective activation or inhibition of specific neuronal subpopulations with millisecond-level spatiotemporal precision, offering a powerful approach to modulate post-injury plasticity. This review synthesizes recent evidence regarding optogenetic interventions for motor rehabilitation in rodent models of ischemic stroke. We detail the multi-level neurobiological mechanisms that drive functional recovery. At the molecular and cellular levels, targeted optical stimulation enhances neurotrophic factor secretion, regulates neurovascular coupling, and modulates glial cell plasticity to create a reparative microenvironment. Circuit-level analysis demonstrates that specific stimulation protocols promote corticospinal tract remodeling and restore the balance of interhemispheric inhibition. Furthermore, modulation of whole-brain network dynamics, particularly the restoration of gamma oscillation rhythmicity, plays a critical role in coordinating motor output and reducing secondary injury. Optogenetics provides crucial mechanistic insights into the neural substrates of stroke recovery. These findings offer a theoretical basis for optimizing parameter selection in existing brain stimulation therapies. While clinical translation faces challenges related to viral vector safety and deep-brain light delivery, precise neuromodulation represents a promising frontier for restoring motor function after cerebral ischemia.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763737","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":"Integrative Analysis Identifies PANoptosis-Associated Molecular Patterns and Immune Alterations in Rat Cerebral Ischemic-Reperfusion Injury.","authors":"Lu Li, Yu Wang, Huili Li, Ying Gao, Lan Luo, Sheng Wang, Mu Jin","doi":"10.1007/s10571-026-01714-w","DOIUrl":"https://doi.org/10.1007/s10571-026-01714-w","url":null,"abstract":"<p><p>Cerebral ischemia-reperfusion (I/R) injury triggers a cascade of neuroinflammatory responses and multiple forms of regulated cell death. PANoptosis, integrating pyroptosis, apoptosis, and necroptosis, has been implicated in inflammatory disorders, but its role in cerebral I/R remains unclear. This study explored the molecular profile and immune relevance of PANoptosis-related genes (PRGs) in rat I/R injury. A rat I/R model was established by transient middle cerebral artery occlusion (MCAO). Transcriptome sequencing identified differentially expressed genes (DEGs) using DESeq2, and PANoptosis-related DEGs (PR-DEGs) were obtained by intersecting with GeneCards-derived PRGs. Functional enrichment (GO, KEGG, Metascape, GSEA), weighted gene co-expression network analysis (WGCNA), and immune infiltration analyses were performed to uncover biological functions and immune features associated with PR-DEGs. Rats subjected to I/R injury showed significant infarction, neurological deficits, and increased TNF-α, IL-1β, and IL-10 expression, along with downregulated Bcl-2 and upregulated CD16 and iNOS, indicating strong inflammatory responses. A total of 51 PR-DEGs were identified, primarily enriched in inflammatory and immune signaling pathways such as TNF, NF-κB, and MAPK. WGCNA revealed the salmon module as most correlated with I/R injury, and hub genes including CASP8, STAT3 were identified. Correlation and immune infiltration analyses demonstrated strong associations between key PR-DEGs and pro-inflammatory immune cells, suggesting a close relationship between PANoptosis-associated gene expression patterns and immune dysregulation in I/R injury. Our findings suggest coordinated activation of PANoptosis-related signaling in cerebral I/R injury. CASP8 and STAT3 were identified as key PR-DEGs associated with I/R, providing a foundation for further mechanistic investigation.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763722","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":"Association Between Blood-Brain Barrier Disruption and Gut Microbiota Dysbiosis in Parkinson's Disease.","authors":"Wanyu Yao, Li Liu, Jiaxin Wang, Shanshan Chen, Chaofan Zhang, Ruiyi Liao, Yiwei Wang, Kunling Ou, Lirong Jiang, Yang Yu, Wei Dong","doi":"10.1007/s10571-026-01738-2","DOIUrl":"https://doi.org/10.1007/s10571-026-01738-2","url":null,"abstract":"","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763749","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":"Mapping the Neurovascular Unit Genetic Architecture of Early-Onset Ischemic Stroke: A Single-Cell Causal Framework for Target Discovery and Therapeutic Translation.","authors":"Qiu-Han Xu, Zhao-Hui Chai, Yu-Ning Zhang, Jian Shen","doi":"10.1007/s10571-026-01722-w","DOIUrl":"https://doi.org/10.1007/s10571-026-01722-w","url":null,"abstract":"","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763707","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":"Celf4 Regulates Excitability of Bushy Cells in the Cochlear Nucleus of the Mouse Brainstem.","authors":"Yige Li, Siyu Qiu, Fang Wang, Zhenghong Bi, Zhiyong Liu, Yingzi He, Geng-Lin Li","doi":"10.1007/s10571-026-01732-8","DOIUrl":"https://doi.org/10.1007/s10571-026-01732-8","url":null,"abstract":"","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763696","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":"Toxic Alpha-Synuclein and the Opening of the Gate: Blood-Brain Barrier Damage and Stepwise Leukocyte Infiltration.","authors":"Piotr Wójcik, Carsten Culmsee, Agata Adamczyk","doi":"10.1007/s10571-026-01733-7","DOIUrl":"https://doi.org/10.1007/s10571-026-01733-7","url":null,"abstract":"","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763699","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":"The Small Chemical Compound Repsox Potentiates Oct4-Driven Astrocyte-to-Neural Stem Cell Reprogramming via Notch1/Hes1/Smurf2 Pathway.","authors":"Xiaoyu Ma, Zijian Liu, Yuqing He, Dandan Zhang, Peng Deng, Lin Li, Xin Li, Junping Li, Quanrui Ma, Hao Yang","doi":"10.1007/s10571-026-01731-9","DOIUrl":"https://doi.org/10.1007/s10571-026-01731-9","url":null,"abstract":"<p><p>Central nervous system (CNS) injury is a prevalent and devastating neurological disorder characterized by progressive and irreversible neuronal loss, leading to persistent neurological deficits. Cell-replacement therapy using pluripotent neural stem cells (NSCs) offers considerable promise for treating CNS injury treatment. Our recent studies have demonstrated that mature astrocytes can be directly reprogrammed to a pluripotent state through specific stimuli. However, acquiring sufficient quantities of functional induced NSCs (iNSCs) derived from astrocytes for clinical applications remains challenging due to the low efficiency and instability in previous methodologies. Consequently, it is of critical importance to improve the reprogramming efficiency of astrocytes into iNSCs. In this study, we showed that the reprogramming of astrocytes into iNSCs via a single transcription factor Oct4 is significantly enhanced by continuous treatment with Repsox, a small molecule inhibitor of transforming growth factor-β (TGF-β) signaling. This enhancement was substantiated by increased efficiency in both reprogramming and conversion processes towards genuine NSCs, as demonstrated by the acquisition of distinctive hallmark NSC properties, including distinct morphological features, self-renewal capacity, expression of NSC-specific markers, and multipotency. Furthermore, the resulting iNSCs successfully differentiated into astrocytes, neurons, and oligodendrocytes. Notably, compared to iNSCs generated by Oct4 alone, Oct4/Repsox-induced NSCs exhibited a greater propensity to give rise to more neurons with neuronal functional properties, and relative fewer glial cells. Mechanistically, the activation of Notch1/Hes1/Smurf2 signaling cascades was involved in this enhanced intricate cell reprogramming events. The efficient reprogramming of astrocyte into iNSCs will provide a promising autologous cell-based therapeutic strategy for patients with CNS injury.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763740","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":"The AMPK-BECN1-System Xc⁻ Pathway in Traumatic Brain Injury: Implications for Exosome-Based Therapy.","authors":"Shenglin Yan, Weican Chen, Yuxin Huang, Nanying Jiang, Yibin Liu, Weifeng Liu","doi":"10.1007/s10571-026-01719-5","DOIUrl":"https://doi.org/10.1007/s10571-026-01719-5","url":null,"abstract":"","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721785","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}