Molecular Neurobiology最新文献

{"title":"SIRT4 Protects Müller Glial Cells Against Apoptosis by Mediating Mitochondrial Dynamics and Oxidative Stress.","authors":"Hongdou Luo, Ming Jin, Haijian Hu, Qian Ying, Piaopiao Hu, Weiwei Sheng, Yi Huang, Ke Xu, Chuming Lu, Xu Zhang","doi":"10.1007/s12035-024-04349-4","DOIUrl":"10.1007/s12035-024-04349-4","url":null,"abstract":"<p><p>SIRT4 is a member of the sirtuin family, which is related to mitochondrial function and possesses antioxidant and regulatory redox effects. Currently, the roles of SIRT4 in retinal Müller glial cells, oxidative stress, and mitochondrial function are still unclear. We confirmed, by immunofluorescence staining, that SIRT4 is located mainly in the mitochondria of retinal Müller glial cells. Using flow cytometry and Western blotting, we analyzed cell apoptosis, intracellular reactive oxygen species (ROS) levels, apoptotic and proapoptotic proteins, mitochondrial dynamics-related proteins, and mitochondrial morphology and number after the overexpression and downregulation of SIRT4 in rMC-1 cells. Neither the upregulation nor the downregulation of SIRT4 alone affected apoptosis. SIRT4 overexpression reduced intracellular ROS, reduced the BAX/BCL2 protein ratio, and increased the L-OPA/S-OPA1 ratio and the levels of the mitochondrial fusion protein MFN2 and the mitochondrial cleavage protein FIS1, increasing mitochondrial fusion. SIRT4 downregulation had the opposite effect. Mitochondria tend to divide after serum starvation for 24 h, and SIRT4 downregulation increases mitochondrial fragmentation and oxidative stress, leading to aggravated cell damage. The mitochondrial division inhibitor Mdivi-1 reduced oxidative stress levels and thus reduced cell damage caused by serum starvation. The overexpression of SIRT4 in rMC-1 cells reduced mitochondrial fragmentation caused by serum starvation, leading to mitochondrial fusion and reduced expression of cleaved caspase-3, thus alleviating the cellular damage caused by oxidative stress. Thus, we speculate that SIRT4 may protect retinal Müller glial cells against apoptosis by mediating mitochondrial dynamics and oxidative stress.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"6683-6702"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633951","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":"Visual Analysis of Research Hotspots and Trends on Mitochondria-Associated Membranes in the Past 20 Years-Focused on Neurodegenerative Diseases.","authors":"Yihang Du, Chenglin Duan, Xueping Zhu, Meng Lyu, Jiafan Chen, Yi Wei, Yuanhui Hu","doi":"10.1007/s12035-025-04722-x","DOIUrl":"10.1007/s12035-025-04722-x","url":null,"abstract":"<p><p>The interaction between mitochondria and the endoplasmic reticulum is mediated by mitochondria-associated endoplasmic reticulum membranes (MAMs), which play a crucial role in regulating intracellular signal transduction and molecular interactions. This study employs bibliometric analysis to examine the research progress on MAMS and identify research hotspots and trends. A total of 1406 publications on MAMs were collected from the Web of Science Core Collection. Software such as CiteSpace, VOSviewer, and Scimago Graphica were utilized in the bibliometric analysis process. This study conducted a bibliometric analysis of over 20 years of MAM research, identifying the countries, institutions, authors, journals, and publications involved in the field. The number of publications on MAMs has been increasing annually since 2010, exhibiting a steady upward trend. The main contributors to this field are the USA, China, and Italy, with the journal Frontiers in Cell and Developmental Biology publishing the most publications. Common keywords include \"endoplasmic reticulum stress,\" \"Ca2 + ,\" \"mitofusin2,\" \"oxidative stress,\" \"apoptosis,\" \"autophagy,\" and \"Alzheimer's disease.\" We found that the role of MAMs in neurodegenerative diseases has aroused great interest among researchers. The associations between calcium homeostasis, autophagy, mitochondrial dysfunction, and cell death with MAMs are also considered research hotspots and show broad research prospects. In addition, changes in MAM-resident proteins, including the mitochondria-ER tethering complex, Mfn2, and Sig-1R, have been highlighted as prominent research directions. The findings provide a comprehensive overview of research on MAMs and valuable insights for researchers, which is helpful for exploring future directions and trends in this field.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7144-7159"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441524","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":"Silica Nanoparticles Induce SH-SY5Y Cells Death Via PARP and Caspase Signaling Pathways.","authors":"Kai Ma, Tiantian Tian, Xinyue Li, Huan Pang, Xiaofan Ning, Meng Li, Jiali Li, Zhixuan Luo, Tianxiang Liu, Mengyue Liu, Mingqian Wang, Chao Zhao, Xiuling Song, Haiying Du, Minghua Jin","doi":"10.1007/s12035-025-04724-9","DOIUrl":"10.1007/s12035-025-04724-9","url":null,"abstract":"<p><p>A growing stream of research indicates that exposure to Silica nanoparticles (SiNPs) can cause nervous system damage, leading to the occurrence of neurodegenerative diseases such as Alzheimer's disease. However, the specific mechanism by which SiNPs cause neuroblast injury remains unclear and requires further research. This study established an in vitro experimental model of SH-SY5Y cells exposed to SiNPs and observed cell growth through an inverted fluorescence microscope. Cell viability was measured using an MTT assay. The intracellular ROS and Ca²⁺ levels were detected by flow cytometry. Cell apoptosis was observed using both Hoechst33342 staining and TUNEL staining. The activities of SOD and ATPase and the content of ATP in the cells were tested by biochemical methods. The genes including parp-1, aif, par, ucp2, vdac and prdx3 were explored using quantitative real-time PCR. The expressions of PARP, AIF, PAR, Caspase-3, Caspase-9 and Cyt C proteins were evaluated by Western Blot. The immunofluorescence technique was used to observe the distribution of Parthanatos-related proteins induced by SiNPs. The results showed that SiNPs reduced cell survival rate, induced excessive ROS and Ca²⁺ overload, decreased SOD activity, ATPase activity, intracellular and mitochondrial ATP content, increased the expression of mitochondrial function and PARP pathway related genes, as well as PARP and Caspase pathway protein expression, ultimately inducing cell apoptosis. As a further test of the roles of PARP and Caspase pathways in SiNPs induced SH-SY5Y cells death, we selected the PARP inhibitor Olaparib and Caspase inhibitor Z-VAD, and the above effects were significantly improved after treatment with the inhibitors. Conclusively, this study confirmed that SiNPs can generate excessive ROS production in SH-SY5Y cells, alter mitochondrial function, and induce cell death through Parthanatos and caspase dependent apoptotic pathways, which can coexist and interact with each other.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7506-7524"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189831","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":"Resveratrol Inhibits VDAC1-Mediated Mitochondrial Dysfunction to Mitigate Pathological Progression in Parkinson's Disease Model.","authors":"Shenglan Feng, Jianjun Gui, Bingqing Qin, Junjie Ye, Qiang Zhao, Ai Guo, Ming Sang, Xiaodong Sun","doi":"10.1007/s12035-024-04234-0","DOIUrl":"10.1007/s12035-024-04234-0","url":null,"abstract":"<p><p>An increase in α-synuclein (α-syn) levels and mutations in proteins associated with mitochondria contribute to the development of familial Parkinson's disease (PD); however, the involvement of α-syn and mitochondria in idiopathic PD remains incompletely understood. The voltage-dependent anion channel I (VDAC1) protein, which serves as a crucial regulator of mitochondrial function and a gatekeeper, plays a pivotal role in governing cellular destiny through the control of ion and respiratory metabolite flux. The ability of resveratrol (RES), which is a potent phytoalexin with antioxidant and anti-inflammatory properties, to regulate VDAC1 in PD is unknown. The objective of this study was to evaluate the role of VDAC1 in the pathological process of PD and to explore the mechanism by which resveratrol protects dopaminergic neurons by regulating VDAC1 to maintain the mitochondrial permeability transition pore (mPTP) and calcium ion balance. The effects of RES on the motor and cognitive abilities of A53T mice were evaluated by using small animal behavioral tests. Various techniques, including immunofluorescence staining, transmission electron microscopy, enzyme-linked immunoadsorption, quantitative polymerase chain reaction (PCR), and Western blotting, among others, were employed to assess the therapeutic impact of RES on neuropathy associated with PD and its potential in regulating mitochondrial VDAC1. The findings showed that RES significantly improved motor and cognitive dysfunction and restored mitochondrial function, thus reducing oxidative stress levels in A53T mice. A significant positive correlation was observed between the protein expression level of VDAC1 and mitochondrial α-syn expression, as well as disease progression, whereas no such correlation was found in VDAC2 and VDAC3. Administration of RES resulted in a significant decrease in the protein expression of VDAC1 and in the protein expression of α-syn both in vivo and in vitro. In addition, we found that RES prevents excessive opening of the mPTP in dopaminergic neurons. This may prevent the abnormal aggregation of α-syn in mitochondria and the release of mitochondrial apoptosis signals. Furthermore, the activation of VDAC1 reversed the resveratrol-induced decrease in the accumulation of α-syn in the mitochondria. These findings highlight the potential of VDAC1 as a therapeutic target for PD and identify the mechanism by which resveratrol alleviates PD-related pathology by modulating mitochondrial VDAC1.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"6636-6654"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180334","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":"Neurotoxicity of Realgar: Crosstalk Between UBXD8-DRP1-Regulated Mitochondrial Fission and PINK1-Parkin-Mediated Mitophagy.","authors":"Rui Feng, Jieyu Liu, Tiantian Yao, Zhao Yang, Hong Jiang","doi":"10.1007/s12035-024-04635-1","DOIUrl":"10.1007/s12035-024-04635-1","url":null,"abstract":"<p><p>Realgar is a toxic mineral medicine containing arsenic that is present in many traditional Chinese medicines. It has been reported that the abuse of drugs containing realgar has potential neurotoxicity, but its mechanism of toxicity has not been fully clarified. In this study, we demonstrated that arsenic in realgar promoted mitochondrial fission via UBXD8-mediated DRP1 translocation to the mitochondria and activated mitophagy via PINK1-Parkin, resulting in mitochondrial dysfunction and nerve cell death in the rat cortex. We used PC12 cells and treated them with inorganic arsenic (iAs). Mdivi-1, a mitochondrial fission inhibitor, and the siRNA UBXD8 or PINK1 were used as interventions to verify the precise mechanism by which arsenic affects realgar-induced mitochondrial instability. The results revealed that the arsenic in realgar accumulated in the brain and led to neurobehavioral abnormalities in the rats. We demonstrated that arsenic in realgar-induced high expression of UBXD8 promoted the translocation of DRP1 to the mitochondria, where it underwent phosphorylation, which led to the over-fission of the mitochondria and mitochondria-mediated apoptosis. Moreover, the over-fission of the mitochondria activates mitophagy, which is self-protective but only partially alleviates apoptosis and mitochondria dysfunction. Our findings revealed the crosstalk between mitochondrial fission and mitophagy in realgar-induced neurotoxicity. These results highlight the role of the transposition of DRP1 by UBXD8 in realgar-induced mitochondrial dysfunction and provide new ideas and data for the study of the mechanism of realgar-induced neurotoxicity.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7041-7053"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682266","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":"Autophagy Induction by Mangiferin Protects Auditory Hair Cells from Ototoxicity.","authors":"Gyeong Min Lim, Gwang-Won Cho, Chul Ho Jang","doi":"10.1007/s12035-025-04751-6","DOIUrl":"10.1007/s12035-025-04751-6","url":null,"abstract":"<p><p>Oxidative stress is a major cause of auditory hair cell degeneration and hearing impairment.Reducing intracellular reactive oxygen species (ROS) levels may help preserve auditory hair cell function. In this study, we explored the otoprotective properties of mangiferin, a xanthonoid extracted from mango leaves, bark, and fruit peels. Our findings indicate that mangiferin protects HEI-OC1 cells against oxidative stress induced by H₂O₂ through modulation of autophagic mechanisms and elimination of ROS. The modulation of proteins linked to autophagy and apoptosis, such as LC3 conversion and SQSTM1 degradation, confirmed this protective effect. Furthermore, auditory brainstem response test and scanning electron microscopy findings indicated that mangiferin effectively mitigates hair cell degeneration in the organ of Corti in guinea pigs subjected to ototoxicity induced by kanamycin and furosemide. Immunohistochemical analysis also provided insights into the effects of mangiferin on ribbon synapses within the cochlea of rats. Both in vitro and in vivo studies demonstrated that mangiferin exerts protective effect against ototoxicity by inducing autophagy.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7903-7914"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425419","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":"Mitochondrial Alterations in Alzheimer's Disease: Insight from the 5xFAD Mouse Model.","authors":"Elif Nedret Keskinoz, Musa Celik, Ezgi Sila Toklucu, Kerem Birisik, Alev Erisir, Devrim Oz-Arslan","doi":"10.1007/s12035-024-04632-4","DOIUrl":"10.1007/s12035-024-04632-4","url":null,"abstract":"<p><p>Mitochondrial dysfunction is increasingly recognized as a key factor in Alzheimer's disease (AD) pathogenesis, but the precise relationship between mitochondrial dynamics and proteinopathies in AD remains unclear. This study investigates the role of mitochondrial dynamics and function in the hippocampal tissue and peripheral blood mononuclear cells (PBMCs) of 5xFAD transgenic mice, as a model of AD. The levels of mitochondrial fusion proteins OPA1 and MFN2 and fission proteins DRP1 and phospho-DRP1 (S616) at 3, 6, and 9 months of age were assessed. Western blot analysis revealed significantly lower levels of OPA1 and MFN2 in the hippocampus of 6- and 9-month-old transgenic (TG) 5xFAD mice compared to controls (CTR), while DRP1 and pDRP1 levels were increased in 9-month-old TG mice. Additionally, MFN2 were decreased in the PBMCs of 9-month-old TG mice, indicating systemic mitochondrial alterations. Ultrastructural analysis of hippocampal tissues showed substantial alterations in mitochondrial morphology, including abnormalities in size and shape, a preponderance of teardrop-shaped mitochondria, and alterations in the somatic mitochondria-ER complex. Notably, mitochondria-associated ER contact sites were more distant in TG mice, suggesting functional impairments. Flow cytometric measurements demonstrated decreased mitochondrial membrane potential and mass, along with increased superoxide production, in the PBMCs of TG mice, particularly at 9 months, highlighting compromised mitochondrial function. Levels of key mitochondrial proteins including VDAC, TOM2O, and mitophagy-related protein PINK1 levels altered in both central and peripheral tissue of TG mice. These findings suggest that mitochondrial dysfunction and altered dynamics are early events in AD development in 5xFAD mice, manifesting in both central and peripheral tissues, and support the notion that mitochondrial abnormalities are an integral component of AD pathology. These insights might lead to the development of targeted therapies that modulate mitochondrial dynamics and function to mitigate AD progression.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7075-7092"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning and Experiments Revealed Key Genes Related to PANoptosis Linked to Drug Prediction and Immune Landscape in Spinal Cord Injury.","authors":"Bo Li, Tao Li, Yibo Cai, Junyao Cheng, Chuyue Zhang, Jianheng Liu, Keran Song, Zheng Wang, Xinran Ji","doi":"10.1007/s12035-025-04717-8","DOIUrl":"10.1007/s12035-025-04717-8","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a severe central nervous system injury without effective therapies. PANoptosis is involved in the development of many diseases, including brain and spinal cord injuries. However, the biological functions and molecular mechanisms of PANoptosis-related genes in spinal cord injury remain unclear. In the bioinformatics analysis of public data of SCI, the differentially expressed genes (DEGs) identified by GSE151371 were hybridized with PANoptosis-related genes (PRGs) to obtain differentially expressed PANoptosis-related genes (DE-PRGs). Through three machine learning algorithms, we obtained the hub genes. Then, we constructed functional analysis, drug prediction, regulatory network construction, and immune infiltrating cell analysis. Finally, the expression of the hub gene was verified in GSE93561, GSE45376, and qRT-PCR analysis. Through the above analysis, 14 DE-PRGs were obtained by intersecting 3582 DEGs with 46 PRGs. Five key hub genes, CASP4, GSDMB, NAIP, NLRC4, and NLRP3, were obtained by 3 machine learning algorithms. All five hub genes were enriched in phagocytosis mediated by FC GAMMA R. The 11 immune cells were significantly different between spinal cord injury (SCI) group and human control (HC) group, such as mast cell and gamma delta T cell. The transcription factor (TF)-hub gene network contained 10-nodes (4 hub genes and 6 TFs) and 8-edges. The miRNA-hub gene network consisting of 5-nodes (3 hub genes and 2 miRNAs) and 3-edges was constructed. Moreover, the CASP4 predicted 1 small molecule drug and NLRP3 predicted 9 small molecule drugs. Finally, the expression of 5 hub genes were significantly different in GSE45376 and GSE93561 (SCI vs. HC) and mice SCI model (Sham vs. SCI). Collectively, we identified 5 hub genes (CASP4, GSDMB, NAIP, NLRC4, and NLRP3) associated with PANoptosis, providing potential directions for treating spinal cord injury.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7364-7379"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Receptor for Advanced Glycation End-products in the Mouse Anterior Cingulate Cortex is Involved in Neuron‒Astrocyte Coupling in Chronic Inflammatory Pain and Anxiety Comorbidity.","authors":"Wei Jiang, Minmin Gong, Linlin Shen, Chenghui Yu, Huaizhen Ruan, Penghui Chen, Shihao Gao, Zhi Xiao","doi":"10.1007/s12035-025-04713-y","DOIUrl":"10.1007/s12035-025-04713-y","url":null,"abstract":"<p><p>Previous studies have shown that astrocyte activation in the anterior cingulate cortex (ACC), accompanied by upregulation of the astrocyte marker S100 calcium binding protein B (S100B), contributes to comorbid anxiety in chronic inflammatory pain (CIP), but the exact downstream mechanism is still being explored. The receptor for advanced glycation end-products (RAGE) plays an important role in chronic pain and psychosis by recognizing ligands, including S100B. Therefore, we speculate that RAGE may be involved in astrocyte regulation of the comorbidity between CIP and anxiety by recognizing S100B. Here, we investigated the potential role of RAGE and the correlation between RAGE and astrocyte regulation in the ACC using a mouse model of complete Freund's adjuvant (CFA)-induced inflammatory pain. We detected substantial upregulation of RAGE expression in ACC neurons when anxiety-like behaviors occurred in CFA-treated mice. The inhibition of RAGE expression decreased the hyperexcitability of ACC neurons and alleviated both hyperalgesia and anxiety in CFA-treated mice. Furthermore, we found that the ACC astrocytic S100B level increased over a similar time course. Intra-ACC application of S100B or downregulation of ACC astrocytic S100B via suppression of astrocyte activation significantly affected RAGE levels and the relative behaviors of CFA-treated mice. Taken together, these findings suggest that the upregulation of ACC neuronal RAGE results from the activation of astrocytic S100B and leads to the maintenance of pain perception and anxiety in the late phase after CFA injection, which may partly explain the mechanism by which ACC neuron‒astrocyte coupling promotes the maintenance of CIP and anxiety comorbidity.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7183-7204"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myricetin Mitigated Sevoflurane-induced Cognitive Dysfunction in Aged-mice Through Inhibiting Histone Deacetylase 2/nuclear Factor Erythroid 2-related Factor 2/heme Oxygenase-1 Signalling-mediated Ferroptosis and Mitochondrial Dysfunction.","authors":"Peng Li, Jingjing Liu, Rui Wang, Fuyang Cao, Jiannan Li, Henglin Wang","doi":"10.1007/s12035-025-04703-0","DOIUrl":"10.1007/s12035-025-04703-0","url":null,"abstract":"<p><p>Sevoflurane anaesthesia induces neurotoxicity and postoperative cognitive dysfunction (POCD) after surgery. This study investigated the roles and potential mechanisms of the natural flavonoid myricetin in sevoflurane-induced cognitive dysfunction. Primary hippocampal neurons were treated with 3% sevoflurane to establish a neuron injury model. Neurons was pre-treated with different concentrations of myricetin, and ferroptosis inhibitor ferrostatin-1 (Fer-1) was used as a positive control. Moreover, mice were anaesthetised with 3% sevoflurane to establish an in-vivo model, and they were pre-treated with 50 or 100 m/kg myricetin. Cell viability and death were determined. Ferroptosis-related markers, including intracellular iron content, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), 4-hydroxy-2-nonenal (4-HNE), glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) protein levels were measured. Myricetin treatment enhanced cell viability and mitigated sevoflurane-induced cell death in the hippocampal neurons. Sevoflurane exposure increased the ROS, MDA and 4-HNE levels and reduced the GSH level, whereas myricetin treatment abrogated these effects. Meanwhile, myricetin treatment restrained sevoflurane-induced increase in intracellular iron content and GPX4 and SLC7A11 protein levels. A high dose of myricetin showed distinct protective effects. Mechanistic studies demonstrated that myricetin treatment reversed sevoflurane-induced histone deacetylase 2 (HDAC2) upregulation and nuclear factor erythroid 2-related factor 2 (Nrf2) deacetylation, thus activating the Nrf2/heme oxygenase-1 (HO-1) signalling. Myricetin treatment mitigated sevoflurane-induced cognitive dysfunction in aged mice by inhibiting hippocampal ferroptosis and mitochondrial dysfunction via the HDAC2/Nrf2/HO-1 signalling pathway. Myricetin may be a treatment option for POCD after surgery.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7776-7791"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399488","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}