Neurochemistry international最新文献

{"title":"Hydrogen restores central tryptophan and metabolite levels and maintains mitochondrial homeostasis to protect rats from chronic mild unpredictable stress damage.","authors":"Jiaxin Li, Gaimei Hao, Yupeng Yan, Ming Li, Gaifen Li, Zhengmin Lu, Zhibo Sun, Yanjing Chen, Haixia Liu, Yukun Zhao, Meng Wu, Xiangxin Bao, Yong Wang, Yubo Li","doi":"10.1016/j.neuint.2024.105914","DOIUrl":"10.1016/j.neuint.2024.105914","url":null,"abstract":"<p><strong>Background and purpose: </strong>The field of hydrogen medicine has garnered extensive attention since Professor Ohsawa established that low concentrations of hydrogen (2%-4%) exert antioxidant effects. The present study aimed to evaluate the therapeutic effect of molecular hydrogen in a CUMS rat model.</p><p><strong>Methods: </strong>A total of 40 SD rats were randomly divided into a control group, a model group, a hydrogen group, and a positive drug group. Four weeks post-modeling, hydrogen inhalation and other treatments were administered. Behavioral, biochemical, and immunohistochemical evaluations were performed after treatment.</p><p><strong>Results: </strong>Hydrogen inhalation alleviated depressive behavior and hippocampal neuronal damage in CUMS rats, as well as restored the levels of neurotransmitters, inflammatory factors, and oxidative stress. Moreover, it maintained mitochondrial homeostasis and up-regulated the expression of PGC-1α, PINK1, and Parkin.</p><p><strong>Conclusions: </strong>The results collectively indicated that hydrogen significantly attenuated CUMS-induced depressive-like behavior and monoamine neurotransmitter deficiency, as well as protected the brain from oxidative stress and inflammatory damage and effectively preserved mitochondrial homeostasis.</p>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":" ","pages":"105914"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anatomizing causal relationships between gut microbiota, plasma metabolites, and epilepsy: A mendelian randomization study.","authors":"Xi Wang, Haowen Duan, Fengfei Lu, Xinyue Yu, Minghan Xie, Peiyi Chen, Junjie Zou, Lijie Gao, Yingqian Cai, Rongqing Chen, Yanwu Guo","doi":"10.1016/j.neuint.2024.105924","DOIUrl":"10.1016/j.neuint.2024.105924","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy causes a heavy disease burden, and the gut microbiota (GM) influences the progression of epilepsy, while plasma metabolites directly or indirectly associated with GM may play a mediating role. However, the causal relationships between epilepsy, GM, and potential metabolite mediators are lack of investigation.</p><p><strong>Methods: </strong>Mendelian randomization (MR) analysis was applied to estimate the effects of GM and plasma metabolites on epilepsy. Genetic instruments were obtained from large-scale genome-wide meta-analysis of GM (n = 5959), plasma metabolites (n = 136,016), and epilepsy (Cases/controls = 12891/312803) of European ancestry. Epilepsy phenotypes included all epilepsy, generalized epilepsy and focal epilepsy from the Finn Gen R10 database. And two-step MR (TSMR) to discover the potential mediating metabolites.</p><p><strong>Results: </strong>In total, we found 19 gut microbial taxa to be causally associated with the risk of epilepsy, among which Omnitrophota phylum had the strongest association (OR, 2.3; P = 0.009) with promoting effect. We also identified 21 plasma metabolites associated with epilepsy, the strongest ones of which are eastotal fatty acids (OR, 1.12; P = 0.001) that exhibited a facilitating effect. We observed indirect effects of free cholesterol to total lipids ratio in large LDL in associations between Fournierella massiliensis species and epilepsy, with a mediated proportion of -3.64% (95%CI, -7.22%∼-0.06%; P = 0.046).</p><p><strong>Conclusion: </strong>This study supports a causal link between Fournierella massiliensis species, free cholesterol to total lipids ratio in large LDL and epilepsy, as well as a mediating effect of free cholesterol to total lipids ratio in large LDL in epilepsy.</p>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":" ","pages":"105924"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A topographic approach to the markers of macrophage/microglia and other cell types in high grade glioma.","authors":"Lucia Lisi, Alessandro Olivi, Gabriella Maria Pia Ciotti, Salvatore Marino, Chiara Ferraro, Grazia Menna, Maria Martire, Giovanni Pennisi, Pierluigi Navarra, Giuseppe Maria Della Pepa","doi":"10.1016/j.neuint.2024.105922","DOIUrl":"10.1016/j.neuint.2024.105922","url":null,"abstract":"<p><p>In glioblastoma, glioma-associated microglia/macrophages (GAMs) represent the major population of tumor infiltrating cells, with up to one half of the cells of the tumor mass. Recent studies have shown that microglia are involved in the maintenance of immunological homeostasis and protection against autoimmunity. However, despite the growing body of evidence on the topic, many aspects are yet to be clarified. In our study, 3 different situations emerged concerning the markers of microglial/macrophage-related and other cell types in GBM patients: i) most of the markers (IBA1, TMEM119, CD206 and CD86) show an ascending gradient from the tumor center to the non-tumor/healthy area of the brain; ii) one marker (CD204) shows a descending gradient, going from the center of the tumor to the non-tumor/healthy brain area; iii) two markers (CD163 and P2RY12) show no gradient. These observations support the idea that the magnitude of the diverted inflammation is a 'extensive' rather than a 'local' phenomenon and that could possibly play a role in disease resistance and relapse.</p>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":" ","pages":"105922"},"PeriodicalIF":4.4,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Celecoxib paradoxically induces COX-2 expression and astrocyte activation through the ERK/JNK/AP-1 signaling pathway in the cerebral cortex of rats.","authors":"Kai-Che Wei, Jun-Ting Lin, Chia-Ho Lin","doi":"10.1016/j.neuint.2024.105926","DOIUrl":"10.1016/j.neuint.2024.105926","url":null,"abstract":"<p><p>Previous studies have shown that celecoxib or NSAID may paradoxically induce cyclooxygenase-2 (COX-2) expression and trigger inflammation-like responses in airway smooth muscle cells and renal mesangial cells. Despite the extensive research on celecoxib, its atypical biological effect on the induction of COX-2 in astroglial cells within the central nervous system (CNS) remains unexplored. In the present study, we investigated the impact of celecoxib on COX-2 and Glial Fibrillary Acidic Protein (GFAP) expression and explored the mechanisms underlying celecoxib-regulated COX-2 expression in cortical astrocytes of rats. Cortical astrocytes were treated with celecoxib (20 μM) for 24 h, resulting in a significant increase in COX-2 expression and up-regulation of GFAP, a marker of astrocyte activation, and the COX-2 induced by celecoxib is functionally active in prostaglandin E2 (PGE2) synthesis. Celecoxib also enhanced LPS-induced COX-2 expression, but its ability to inhibit PGE2 synthesis decreased at higher concentrations. Celecoxib induced phosphorylation of Extracellular signal-regulated Kinase (ERK) and c-Jun N-terminal Kinase (JNK) but not p38 Mitogen-Activated Protein Kinase (p38 MAPK), and inhibition of activity of ERK and JNK by U0126 and SP600125 effectively blocked COX-2 and GFAP induction by celecoxib. Celecoxib increased the accumulation of transcription factor AP-1 (composed of phosphorylated c-Jun and c-fos) in the nucleus. Inhibition of AP-1 activity with SR11302 significantly prevented celecoxib-induced COX-2 and GFAP expression. Additionally, the inhibiting activity of ERK and JNK can effectively suppress AP-1 expression and activity induced by celecoxib. These findings demonstrated that celecoxib induces COX-2 expression and astrocyte activation through the ERK/JNK/AP-1 signaling pathway, highlighting its potential effect in modulating inflammatory responses in the central nervous system.</p>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":" ","pages":"105926"},"PeriodicalIF":4.4,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferritinophagy promotes microglia ferroptosis to aggravate neuroinflammation induced by cerebral ischemia-reperfusion injury via activation of the cGAS-STING signaling pathway.","authors":"Haijing Sui, Zhenyu Sun, Chang Liu, Hongjie Xi","doi":"10.1016/j.neuint.2024.105920","DOIUrl":"10.1016/j.neuint.2024.105920","url":null,"abstract":"<p><p>Cerebral ischemia-reperfusion injury (CIRI) is a common and serious complication of reperfusion therapy in patients with ischemic stroke (IS). The regulation of microglia-mediated neuroinflammation to control CIRI has garnered considerable attention. The balance of iron metabolism is key to maintaining the physiological functions of microglia. Nuclear Receptor Coactivator 4 (NCOA4)-mediated ferritinophagy, an important pathway in regulating iron metabolism, is a promising intervention target. However, studies on the impacts of ferritinophagy on microglia-mediated neuroinflammation are lacking. This study aimed to identify potential treatments for CIRI-induced neuroinflammation by focusing on ferritinophagy and the specific mechanisms whereby iron metabolism regulates microglia-mediated neuroinflammation. CIRI induced the activation of ferritinophagy in microglia, characterized by the upregulation of NCOA4, downregulation of Ferritin Heavy Chain 1 (FTH1), and increased intracellular iron levels. This activation contributes to increased ferroptosis, oxidative stress, and the release of inflammatory factors. Silencing NCOA4 or application of the ferroptosis-specific inhibitor Ferrostatin-1 (Fer-1) effectively suppressed the CIRI-induced damage in vivo and in vitro. While Fer-1 addition did not inhibit the CIRI-activated ferritinophagy, it did partially reverse the alleviation of NCOA4 depletion-induced neuroinflammation, suggesting that ferroptosis is an essential intermediate step in ferritinophagy-induced neuroinflammatory damage. Furthermore, using IS-related transcriptomic data, the cGAS-STING pathway was identified as a crucial mechanism connecting ferritinophagy and ferroptosis. Specific inhibition of the cGAS-STING pathway reduced ferritinophagy-induced ferroptosis and neuroinflammation. In summary, our results indicated that ferritinophagy activates the cGAS-STING signaling pathway, which promotes the inflammatory response and oxidative stress in microglia in a ferroptosis-dependent manner, thereby exacerbating CIRI-induced neuroinflammation. These findings provide theoretical support for the clinical treatment of CIRI.</p>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":" ","pages":"105920"},"PeriodicalIF":4.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogen inhalation exerts anti-seizure effects by preventing oxidative stress and inflammation in the hippocampus in a rat model of kainic acid-induced seizures.","authors":"Tzu-Kang Lin, Ming-Shang Pai, Kun-Chieh Yeh, Chi-Feng Hung, Su-Jane Wang","doi":"10.1016/j.neuint.2024.105925","DOIUrl":"https://doi.org/10.1016/j.neuint.2024.105925","url":null,"abstract":"<p><p>Hydrogen gas (H₂) is an antioxidant with demonstrated neuroprotective efficacy. In this study, we administered H₂ via inhalation to rats to evaluate its effects on seizures induced by kainic acid (KA) injection and the underlying mechanism. The animals were intraperitoneally injected with KA (15 mg/kg) to induce seizures. H₂ was inhaled 2 h once a day for 5 days before KA administration. The seizure activity was evaluated using Racine's convulsion scale and electroencephalography (EEG). Neuronal cell loss, glial cell activation, and the levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, CCL2, and CCL3), reactive oxygen species (ROS) and nuclear factor erythroid 2-related factor 2 (Nrf2) in the hippocampus were assessed. The cerebral blood flow of the rats was also evaluated. The results revealed that KA-treated rats presented increased seizure intensity; increased neuronal loss and astrocyte activation; increased levels of ROS, TNF-α, IL-1β, IL-6, CCL2, and CCL3; and reduced Nrf2 phosphorylation levels. Pretreatment with H₂ inhalation significantly attenuated seizure intensity; prevented neuronal loss; decreased microglial and astrocytic activation; decreased ROS, TNF-α, IL-1β, IL-6, CCL2 and CCL3 levels; and increased Nrf2 levels. Inhalation of H₂ also prevented the KA-induced decrease in cerebral blood flow. These results suggest that pretreatment with H₂ inhalation ameliorates KA-induced seizures and inhibits the inflammatory response and oxidative stress, which protects neurons.</p>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"183 ","pages":"105925"},"PeriodicalIF":4.4,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Previous strength training attenuates ouabain-induced bipolar disorder-related behaviors and memory deficits in rats: Involvement of hippocampal ERK/CREB and PI3K/AKT/mTOR pathways.","authors":"Luan Machado Maidana, Jozyê Milena da Silva Guerra, Adson Souza-Pereira, Marizabel Parente Lins, Mayckel Jean Moreira-Silva, Eduarda Goulart Paiva, Douglas Buchmann Godinho, Luis Fernando Freire Royes, Leonardo Magno Rambo","doi":"10.1016/j.neuint.2024.105919","DOIUrl":"10.1016/j.neuint.2024.105919","url":null,"abstract":"<p><p>Bipolar disorder (BD) is a central nervous system condition that is typified by fluctuations in mood, oscillating between depressive and manic, and/or hypomanic episodes. The objective of this study was to test the hypothesis that strength training may act as a potent protector against behavioral and neurochemical changes induced by BD. A strength training protocol was performed with adult male Wistar rats, and seven days following the conclusion of training, a single ouabain injection was administered. Following ouabain administration, the animals were subjected to behavioral tests after the seventh (manic period) and fourteenth (depressive period) days. Subsequently, rats were euthanized and the hippocampus was collected for western blotting assays. We demonstrated that strength training provided protection against ouabain-induced behavioral changes, both during the manic and depressive periods, including increased locomotor activity, risk-taking and aggressive-like behaviors, and impaired memory performance. Furthermore, physical training protected against ouabain-induced decrease of neurogenesis/neuroplasticity-related pathways, including BDNF/TrKB/ERK/CREB and PI3K/AKT/mTOR/p70S6K. These findings suggest that strength training has a protective effect, attenuating or preventing BD-induced deficits, and may have therapeutic potential as an adjuvant treatment for this patient population in the future.</p>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":" ","pages":"105919"},"PeriodicalIF":4.4,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain endocannabinoid control of metabolic and non-metabolic feeding behaviors.","authors":"Maoxing Zhang, Qingyu Wang, Ying Wang","doi":"10.1016/j.neuint.2024.105921","DOIUrl":"10.1016/j.neuint.2024.105921","url":null,"abstract":"<p><p>The central endocannabinoid (eCB) system in brain shows a crucial role in the regulation of feeding behaviors, influencing both metabolic and non-metabolic mechanisms of appetite control, which has been paid much attention. Although there are already many review articles discussing eCB modulation of feeding behaviors, our paper attempts to summarize the recent advancements through synapses, circuits, and network in brain. Our focus is on the dual role of eCB signalling in regulating metabolic energy balance and hedonic reward-related feeding. In the context of metabolic regulation of feeding behaviors, eCBs affect the hypothalamic circuits that balance hunger and satiety through signal integration related to energy status and nutrient availability. Dysregulation of this system can contribute to metabolic disorders such as obesity and anorexia. In non-metabolic feeding, the eCB system influences the hedonic aspects of eating by modulating reward pathways, including the mesolimbic system and the olfactory bulb, critical for motivating food intake and processing sensory cues. This review also explores therapeutic strategies targeting the eCB system, including cannabinoid receptor antagonists and eCB hydrolase enzyme inhibitors, which hold promise for treating conditions associated with appetite dysregulation and eating disorders. By synthesizing recent findings, we aim to highlight the intricate mechanisms through which the eCB system affects feeding behavior and to propose future directions for research and therapeutic intervention in the realm of appetite control and eating disorders.</p>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":" ","pages":"105921"},"PeriodicalIF":4.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VNS facilitates the neurological function recovery after ischemia/reperfusion injury by regulating the A1/A2 polarization of astrocytes through the NMU-NMUR2 pathway.","authors":"Xia Jiang, Wendi Yang, Gang Liu, Hao Tang, Renzi Zhang, Lina Zhang, Changqing Li, Sheng Li","doi":"10.1016/j.neuint.2024.105918","DOIUrl":"10.1016/j.neuint.2024.105918","url":null,"abstract":"<p><p>Stroke is the second leading cause of death worldwide. Although conventional treatments such as thrombolysis and mechanical thrombectomy are effective, their narrow therapeutic window limits long-term neurological recovery. Previous studies have shown that vagus nerve stimulation (VNS) enhances neurological recovery after ischemia/reperfusion (I/R) injury, and neuromedin U (NMU) has neuroprotective effects. This study used a mouse model of cerebral I/R injury to investigate the potential mechanisms of NMU in VNS-mediated neurological improvement. The study consisted of two parts: first, assessing the dynamic expression of NMU and NMUR2, which peaked on day 14 post-I/R. NMUR2 was primarily localized in astrocytes, suggesting that the NMU-NMUR2 signaling pathway plays an important role in astrocyte regulation. Next, interventions with VNS, NMU, and R-PSOP + VNS were conducted to evaluate the role of this pathway in VNS-mediated recovery. The results showed that VNS significantly upregulated NMU and NMUR2 expression, which was blocked by the NMUR2 antagonist R-PSOP. VNS and NMU treatment increased the proportion of A2 astrocytes, reduced A1 astrocytes, and enhanced the expression of VEGF and BDNF, all of which were also blocked by R-PSOP. These findings indicate that the \"VNS-NMU-NMUR2-astrocyte A1/A2 polarization-VEGF/BDNF pathway\" plays a crucial role in promoting neurovascular remodeling, axonal and dendritic regeneration, and synaptic plasticity, thereby contributing to functional recovery.</p>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":" ","pages":"105918"},"PeriodicalIF":4.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leptin deficiency leads to nerve degeneration and impairs axon remyelination by inducing Schwann cell apoptosis and demyelination in type 2 diabetic peripheral neuropathy in rats","authors":"Yuan-Shuo Hsueh ,&nbsp;Szu-Han Chen ,&nbsp;Wan-Ling Tseng ,&nbsp;Sheng-Che Lin ,&nbsp;De-Quan Chen ,&nbsp;Chih-Chung Huang ,&nbsp;Yuan-Yu Hsueh","doi":"10.1016/j.neuint.2024.105908","DOIUrl":"10.1016/j.neuint.2024.105908","url":null,"abstract":"<div><div>Diabetic peripheral neuropathy, characterized by symptoms such as paresthesia, neuropathic pain, and potential lower limb amputation, poses significant clinical management challenges. Recent studies suggest that chronic hyperglycemia-induced Schwann cells (SCs) apoptosis contributes to neurodegeneration and impaired nerve regeneration, but the detailed mechanisms are still unknown. Our study investigated a mixed-sex type 2 diabetes mellitus (T2DM) rat model using leptin knockout (KO) to simulate obesity and diabetes-related conditions. Through extensive assessments, including mechanical allodynia, electrophysiology, and microcirculation analyses, along with myelin degradation studies in KO versus wild-type rats, we focused on apoptosis, autophagy, and SCs dedifferentiation in the sciatic nerve and examined nerve regeneration in KO rats. KO rats exhibited notable reductions in mechanical withdrawal force, prolonged latency, decreased compound muscle action potential (CMAP) amplitude, reduced microcirculation, myelin sheath damage, and increases in apoptosis, autophagy, and SCs dedifferentiation. Moreover, leptin KO was found to impair peripheral nerve regeneration postinjury, as indicated by reduced muscle weight, lower CMAP amplitude, extended latency, and decreased remyelination and SCs density. These findings underscore the effectiveness of the T2DM rat model in clarifying the impact of leptin KO on SCs apoptosis, dedifferentiation, and demyelination, providing valuable insights into new therapeutic avenues for treating T2DM-induced peripheral neuropathy.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"182 ","pages":"Article 105908"},"PeriodicalIF":4.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}