Vestibular compensation is the natural process of recovery that occurs with acute peripheral vestibular lesion. Here, we summarize the current understanding of the mechanisms underlying vestibular compensation, focusing on the role of the medial vestibular nucleus (MVN), the central hub of the vestibular system, and its associated neural networks. The disruption of neural activity balance between the bilateral MVNs underlies the vestibular symptoms after unilateral vestibular damage, and this balance disruption can be partially reversed by the mutual inhibitory projections between the bilateral MVNs, and their top-down regulation by other brain regions via different neurotransmitters. However, the detailed mechanism of how MVN is involved in vestibular compensation and regulated remains largely unknown. A deeper understanding of the vestibular neural network and the neurotransmitter systems involved in vestibular compensation holds promise for improving treatment outcomes and developing more effective interventions for vestibular disorders.
{"title":"Advanced progress of vestibular compensation in vestibular neural networks","authors":"Jun Wang, Yuejin Zhang, Huajing Yang, E. Tian, Zhaoqi Guo, Jingyu Chen, Caijuan Qiao, Hongqun Jiang, Jiaqi Guo, Zhanghong Zhou, Qing Luo, Shiyu Shi, Hongyi Yao, Yisheng Lu, Sulin Zhang","doi":"10.1111/cns.70037","DOIUrl":"https://doi.org/10.1111/cns.70037","url":null,"abstract":"<p>Vestibular compensation is the natural process of recovery that occurs with acute peripheral vestibular lesion. Here, we summarize the current understanding of the mechanisms underlying vestibular compensation, focusing on the role of the medial vestibular nucleus (MVN), the central hub of the vestibular system, and its associated neural networks. The disruption of neural activity balance between the bilateral MVNs underlies the vestibular symptoms after unilateral vestibular damage, and this balance disruption can be partially reversed by the mutual inhibitory projections between the bilateral MVNs, and their top-down regulation by other brain regions via different neurotransmitters. However, the detailed mechanism of how MVN is involved in vestibular compensation and regulated remains largely unknown. A deeper understanding of the vestibular neural network and the neurotransmitter systems involved in vestibular compensation holds promise for improving treatment outcomes and developing more effective interventions for vestibular disorders.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yun-zhu Pan, Zuliyaer Talifu, Xiao-xin Wang, Han Ke, Chun-jia Zhang, Xin Xu, De-gang Yang, Yan Yu, Liang-jie Du, Feng Gao, Jian-Jun Li
<div> <section> <h3> Aim</h3> <p>We aimed to explore whether the combination of CLP290 and bumetanide maximally improves neuropathic pain following spinal cord injury (SCI) and its possible molecular mechanism.</p> </section> <section> <h3> Methods</h3> <p>Rats were randomly divided into five groups: Sham, SCI + vehicle, SCI + CLP290, SCI + bumetanide, and SCI + combination (CLP290 + bumetanide). Drug administration commenced on the 7th day post-injury (7 dpi) and continued for 14 days. All rats underwent behavioral assessments for 56 days to comprehensively evaluate the effects of interventions on mechanical pain, thermal pain, cold pain, motor function, and other relevant parameters. Electrophysiological assessments, immunoblotting, and immunofluorescence detection were performed at different timepoints post-injury, with a specific focus on the expression and changes of KCC2 and NKCC1 proteins in the lumbar enlargement of the spinal cord.</p> </section> <section> <h3> Results</h3> <p>CLP290 and bumetanide alleviated SCI-associated hypersensitivity and locomotor function, with the combination providing enhanced recovery. The combined treatment group exhibited the most significant improvement in restoring Rate-Dependent Depression (RDD) levels. In the combined treatment group and the two individual drug administration groups, the upregulation of potassium chloride cotransporter 2 (K<sup>+</sup>-Cl<sup>−</sup>cotransporter 2, KCC2) expression and downregulation of sodium potassium chloride cotransporter 1 (Na<sup>+</sup>-K<sup>+</sup>-Cl<sup>−</sup>cotransporter 1, NKCC1) expression in the lumbar enlargement area resulted in a significant increase in the KCC2/NKCC1 ratio compared to the SCI + vehicle group, with the most pronounced improvement seen in the combined treatment group. Compared to the SCI + vehicle group, the SCI + bumetanide group showed no significant paw withdrawal thermal latency (PWTL) improvement at 21 and 35 dpi, but a notable enhancement at 56 dpi. In contrast, the SCI + CLP290 group significantly improved PWTL at 21 days, with non-significant changes at 35 and 56 days. At 21 dpi, KCC2 expression was marginally higher in monotherapy groups versus SCI + vehicle, but not significantly. At 56 dpi, only the SCI + bumetanide group showed a significant difference in KCC2 expression compared to the control group.</p> </section> <section> <h3> Conclusion</h3> <p>Combined application of CLP290 and bumetanide effectively increases the ratio of KCC2/NKCC1, restores RDD levels, enhances GABA<sub>A</sub> receptor-mediated inhibitory function
{"title":"Combined use of CLP290 and bumetanide alleviates neuropathic pain and its mechanism after spinal cord injury in rats","authors":"Yun-zhu Pan, Zuliyaer Talifu, Xiao-xin Wang, Han Ke, Chun-jia Zhang, Xin Xu, De-gang Yang, Yan Yu, Liang-jie Du, Feng Gao, Jian-Jun Li","doi":"10.1111/cns.70045","DOIUrl":"https://doi.org/10.1111/cns.70045","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>We aimed to explore whether the combination of CLP290 and bumetanide maximally improves neuropathic pain following spinal cord injury (SCI) and its possible molecular mechanism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Rats were randomly divided into five groups: Sham, SCI + vehicle, SCI + CLP290, SCI + bumetanide, and SCI + combination (CLP290 + bumetanide). Drug administration commenced on the 7th day post-injury (7 dpi) and continued for 14 days. All rats underwent behavioral assessments for 56 days to comprehensively evaluate the effects of interventions on mechanical pain, thermal pain, cold pain, motor function, and other relevant parameters. Electrophysiological assessments, immunoblotting, and immunofluorescence detection were performed at different timepoints post-injury, with a specific focus on the expression and changes of KCC2 and NKCC1 proteins in the lumbar enlargement of the spinal cord.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CLP290 and bumetanide alleviated SCI-associated hypersensitivity and locomotor function, with the combination providing enhanced recovery. The combined treatment group exhibited the most significant improvement in restoring Rate-Dependent Depression (RDD) levels. In the combined treatment group and the two individual drug administration groups, the upregulation of potassium chloride cotransporter 2 (K<sup>+</sup>-Cl<sup>−</sup>cotransporter 2, KCC2) expression and downregulation of sodium potassium chloride cotransporter 1 (Na<sup>+</sup>-K<sup>+</sup>-Cl<sup>−</sup>cotransporter 1, NKCC1) expression in the lumbar enlargement area resulted in a significant increase in the KCC2/NKCC1 ratio compared to the SCI + vehicle group, with the most pronounced improvement seen in the combined treatment group. Compared to the SCI + vehicle group, the SCI + bumetanide group showed no significant paw withdrawal thermal latency (PWTL) improvement at 21 and 35 dpi, but a notable enhancement at 56 dpi. In contrast, the SCI + CLP290 group significantly improved PWTL at 21 days, with non-significant changes at 35 and 56 days. At 21 dpi, KCC2 expression was marginally higher in monotherapy groups versus SCI + vehicle, but not significantly. At 56 dpi, only the SCI + bumetanide group showed a significant difference in KCC2 expression compared to the control group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Combined application of CLP290 and bumetanide effectively increases the ratio of KCC2/NKCC1, restores RDD levels, enhances GABA<sub>A</sub> receptor-mediated inhibitory function ","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142230921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ischemic stroke is a major cause of disability and mortality worldwide. Transcranial direct current stimulation (tDCS) and isoflurane (ISO) preconditioning exhibit neuroprotective properties. However, it remains unclear whether tDCS enhances the protective effect of ISO preconditioning on ischemic stroke, and the underlying mechanisms are yet to be clarified.
Method
A model of middle cerebral artery occlusion (MCAO), a rat ischemia–reperfusion (I/R) injury model, and an in vitro oxygen–glucose deprivation/re-oxygenation (O/R) model of ischemic injury were developed. ISO preconditioning and tDCS were administered daily for 7 days before MCAO modeling. Triphenyltetrazolium chloride staining, modified neurological severity score, and hanging-wire test were conducted to assess infarct volume and neurological outcomes. Untargeted metabolomic experiments, adeno-associated virus, lentiviral vectors, and small interfering RNA techniques were used to explore the underlying mechanisms.
Results
tDCS/DCS enhanced the protective effects of ISO pretreatment on I/R injury-induced brain damage. This was evidenced by reduced infarct volume and improved neurological outcomes in rats with MCAO, as well as decreased cortical neuronal death after O/R injury. Untargeted metabolomic experiments identified oxidative phosphorylation (OXPHOS) as a critical pathological process for ISO-mediated neuroprotection from I/R injury. The combination of tDCS/DCS with ISO preconditioning significantly inhibited I/R injury-induced OXPHOS. Mechanistically, Akirin2, a small nuclear protein that regulates cell proliferation and differentiation, was found to decrease in the cortex of rats with MCAO and in cortical primary neurons subjected to O/R injury. Akirin2 functions upstream of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). tDCS/DCS was able to further upregulate Akirin2 levels and activate the Akirin2/PTEN signaling pathway in vivo and in vitro, compared with ISO pretreatment alone, thereby contributing to the improvement of cerebral I/R injury.
Conclusion
tDCS treatment enhances the neuroprotective effects of ISO preconditioning on ischemic stroke by inhibiting oxidative stress and activating Akirin2-PTEN signaling pathway, highlighting potential of combination therapy in ischemic stroke.
目的 缺血性中风是全球致残和致死的主要原因。经颅直流电刺激（tDCS）和异氟烷（ISO）预处理具有神经保护特性。然而，经颅直流电刺激（tDCS）是否能增强异氟烷预处理对缺血性中风的保护作用仍不清楚，其潜在机制也有待明确。 方法 建立了大脑中动脉闭塞（MCAO）模型、大鼠缺血再灌注（I/R）损伤模型和体外氧-葡萄糖剥夺/再氧合（O/R）缺血性损伤模型。在MCAO模型建立前，每天进行ISO预处理和tDCS治疗7天。通过三苯基氯化四氮唑染色、改良神经系统严重程度评分和悬丝试验来评估梗死体积和神经系统预后。非靶向代谢组学实验、腺相关病毒、慢病毒载体和小干扰 RNA 技术被用来探索潜在的机制。 结果 tDCS/DCS 增强了 ISO 预处理对 I/R 损伤诱导的脑损伤的保护作用。MCAO大鼠脑梗塞体积缩小、神经功能改善以及O/R损伤后皮质神经元死亡减少都证明了这一点。非靶向代谢组实验确定氧化磷酸化（OXPHOS）是 ISO 介导的 I/R 损伤神经保护的关键病理过程。将 tDCS/DCS 与 ISO 预处理相结合可显著抑制 I/R 损伤诱导的 OXPHOS。从机理上讲，研究发现Akirin2是一种调节细胞增殖和分化的小核蛋白，它在MCAO大鼠的大脑皮层和受到O/R损伤的大脑皮层初级神经元中减少。与单独使用 ISO 预处理相比，tDCS/DCS 能够进一步上调体内和体外 Akirin2 水平并激活 Akirin2/PTEN 信号通路，从而有助于改善脑 I/R 损伤。 结论 tDCS治疗通过抑制氧化应激和激活Akirin2-PTEN信号通路，增强了ISO预处理对缺血性中风的神经保护作用，凸显了联合疗法在缺血性中风中的潜力。
{"title":"Transcranial direct current stimulation enhances the protective effect of isoflurane preconditioning on cerebral ischemia/reperfusion injury: A new mechanism associated with the nuclear protein Akirin2","authors":"Xiangyi Kong, Wenyuan Lyu, Xiaojie Lin, Hao Feng, Lin Xu, Chengwei Li, Xinyi Sun, Chunlong Lin, Jianjun Li, Penghui Wei","doi":"10.1111/cns.70033","DOIUrl":"https://doi.org/10.1111/cns.70033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Ischemic stroke is a major cause of disability and mortality worldwide. Transcranial direct current stimulation (tDCS) and isoflurane (ISO) preconditioning exhibit neuroprotective properties. However, it remains unclear whether tDCS enhances the protective effect of ISO preconditioning on ischemic stroke, and the underlying mechanisms are yet to be clarified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>A model of middle cerebral artery occlusion (MCAO), a rat ischemia–reperfusion (I/R) injury model, and an in vitro oxygen–glucose deprivation/re-oxygenation (O/R) model of ischemic injury were developed. ISO preconditioning and tDCS were administered daily for 7 days before MCAO modeling. Triphenyltetrazolium chloride staining, modified neurological severity score, and hanging-wire test were conducted to assess infarct volume and neurological outcomes. Untargeted metabolomic experiments, adeno-associated virus, lentiviral vectors, and small interfering RNA techniques were used to explore the underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>tDCS/DCS enhanced the protective effects of ISO pretreatment on I/R injury-induced brain damage. This was evidenced by reduced infarct volume and improved neurological outcomes in rats with MCAO, as well as decreased cortical neuronal death after O/R injury. Untargeted metabolomic experiments identified oxidative phosphorylation (OXPHOS) as a critical pathological process for ISO-mediated neuroprotection from I/R injury. The combination of tDCS/DCS with ISO preconditioning significantly inhibited I/R injury-induced OXPHOS. Mechanistically, Akirin2, a small nuclear protein that regulates cell proliferation and differentiation, was found to decrease in the cortex of rats with MCAO and in cortical primary neurons subjected to O/R injury. Akirin2 functions upstream of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). tDCS/DCS was able to further upregulate Akirin2 levels and activate the Akirin2/PTEN signaling pathway in vivo and in vitro, compared with ISO pretreatment alone, thereby contributing to the improvement of cerebral I/R injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>tDCS treatment enhances the neuroprotective effects of ISO preconditioning on ischemic stroke by inhibiting oxidative stress and activating Akirin2-PTEN signaling pathway, highlighting potential of combination therapy in ischemic stroke.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chengliang Pan, Zhilin Ji, Qingxuan Wang, Zhao Zhang, Zhenchuan Wang, Chen Li, Shan Lu, Pengfei Ge
Background
Copper is an essential trace element for biological systems, as it plays a critical role in the activity of various enzymes and metabolic processes. However, the dysregulation of copper homeostasis is closely associated with the onset and progression of numerous diseases. In recent years, copper-induced cell death, a novel form of cellular demise, has garnered significant attention. This process is characterized by the abnormal accumulation of intracellular copper ions, leading to cellular dysfunction and eventual cell death. Copper toxicity occurs through the interaction of copper with acylated enzymes in the tricarboxylic acid (TCA) cycle. This interaction results in subsequent protein aggregation, causing proteotoxic stress and ultimately resulting in cell death. Despite the promise of these findings, the detailed mechanisms and broader implications of cuproptosis remain underexplored. Therefore, our study aimed to investigate the role of copper in cell death and autophagy, focusing on the molecular mechanisms of cuproptosis. We also aimed to discuss recent advancements in copper-related research across various diseases and tumors, providing insights for future studies and potential therapeutic applications.
Main Body
This review delves into the biological significance of copper metabolism and the molecular mechanisms underlying copper-induced cell death. Furthermore, we discuss the role of copper toxicity in the pathogenesis of various diseases, emphasizing recent advancements in the field of oncology. Additionally, we explore the therapeutic potential of targeting copper toxicity.
Conclusion
The study highlights the need for further research to explore alternative pathways of copper-induced cell death, detailed mechanisms of cuproptosis, and biomarkers for copper poisoning. Future research should focus on exploring the molecular mechanisms of cuproptosis, developing new therapeutic strategies, and verifying their safety and efficacy in clinical trials.
{"title":"Cuproptosis: Mechanisms, biological significance, and advances in disease treatment—A systematic review","authors":"Chengliang Pan, Zhilin Ji, Qingxuan Wang, Zhao Zhang, Zhenchuan Wang, Chen Li, Shan Lu, Pengfei Ge","doi":"10.1111/cns.70039","DOIUrl":"https://doi.org/10.1111/cns.70039","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Copper is an essential trace element for biological systems, as it plays a critical role in the activity of various enzymes and metabolic processes. However, the dysregulation of copper homeostasis is closely associated with the onset and progression of numerous diseases. In recent years, copper-induced cell death, a novel form of cellular demise, has garnered significant attention. This process is characterized by the abnormal accumulation of intracellular copper ions, leading to cellular dysfunction and eventual cell death. Copper toxicity occurs through the interaction of copper with acylated enzymes in the tricarboxylic acid (TCA) cycle. This interaction results in subsequent protein aggregation, causing proteotoxic stress and ultimately resulting in cell death. Despite the promise of these findings, the detailed mechanisms and broader implications of cuproptosis remain underexplored. Therefore, our study aimed to investigate the role of copper in cell death and autophagy, focusing on the molecular mechanisms of cuproptosis. We also aimed to discuss recent advancements in copper-related research across various diseases and tumors, providing insights for future studies and potential therapeutic applications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Main Body</h3>\u0000 \u0000 <p>This review delves into the biological significance of copper metabolism and the molecular mechanisms underlying copper-induced cell death. Furthermore, we discuss the role of copper toxicity in the pathogenesis of various diseases, emphasizing recent advancements in the field of oncology. Additionally, we explore the therapeutic potential of targeting copper toxicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study highlights the need for further research to explore alternative pathways of copper-induced cell death, detailed mechanisms of cuproptosis, and biomarkers for copper poisoning. Future research should focus on exploring the molecular mechanisms of cuproptosis, developing new therapeutic strategies, and verifying their safety and efficacy in clinical trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142230920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Extended fasting–postprandial switch intermitting time has been shown to affect Alzheimer's disease (AD). Few studies have investigated the cerebral perfusion response to fasting–postprandial metabolic switching (FMS) in AD patients. We aimed to evaluate the cerebral perfusion response to FMS in AD patients.
Methods
In total, 30 AD patients, 32 mild cognitive impairment (MCI) patients, and 30 healthy control individuals (HCs) were included in the quantification of cerebral perfusion via cerebral blood flow (CBF). The cerebral perfusion response to FMS was defined as the difference (ΔCBF) between fasting and postprandial CBF.
Results
Patients with AD had a regional negative ΔCBF in the anterior temporal lobe, part of the occipital lobe and the parietal lobe under FMS stimulation, whereas HCs had no significant ΔCBF. The AD patients had lower ΔCBF values in the right anterior temporal lobe than the MCI patients and HCs. ΔCBF in the anterior temporal lobe was negatively correlated with cognitive severity and cognitive reserve factors in AD patients.
Conclusions
AD patients exhibited a poor ability to maintain cerebral perfusion homeostasis under FMS stimulation. The anterior temporal lobe is a distinct area that responds to FMS in AD patients and negatively correlates with cognitive function.
{"title":"Neuroimaging analysis reveals distinct cerebral perfusion responses to fasting-postprandial metabolic switching in Alzheimer's disease patients","authors":"Runzhi Li, Zhizheng Zhuo, Zeshan Yao, Zhaohui Li, Yanli Wang, Jiwei Jiang, Linlin Wang, Wenyi Li, Yanling Zhang, Jun Sun, Junjie Li, Yunyun Duan, Yi Liu, Hongyuan Shao, Yang li, Yechuan Zhang, Jinglong Chen, Hanping Shi, Hui Huang, Yaou Liu, Jun Xu","doi":"10.1111/cns.70014","DOIUrl":"https://doi.org/10.1111/cns.70014","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Extended fasting–postprandial switch intermitting time has been shown to affect Alzheimer's disease (AD). Few studies have investigated the cerebral perfusion response to fasting–postprandial metabolic switching (FMS) in AD patients. We aimed to evaluate the cerebral perfusion response to FMS in AD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In total, 30 AD patients, 32 mild cognitive impairment (MCI) patients, and 30 healthy control individuals (HCs) were included in the quantification of cerebral perfusion via cerebral blood flow (CBF). The cerebral perfusion response to FMS was defined as the difference (ΔCBF) between fasting and postprandial CBF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with AD had a regional negative ΔCBF in the anterior temporal lobe, part of the occipital lobe and the parietal lobe under FMS stimulation, whereas HCs had no significant ΔCBF. The AD patients had lower ΔCBF values in the right anterior temporal lobe than the MCI patients and HCs. ΔCBF in the anterior temporal lobe was negatively correlated with cognitive severity and cognitive reserve factors in AD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>AD patients exhibited a poor ability to maintain cerebral perfusion homeostasis under FMS stimulation. The anterior temporal lobe is a distinct area that responds to FMS in AD patients and negatively correlates with cognitive function.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nearly half of patients with diabetes experience diabetic peripheral neuropathy (DPN), resulting in a mere 53% survival rate within 3 years. Aberrations in coagulation function have been implicated in the pathogenesis of microvascular complications, prompting the need for a thorough investigation into its role as a contributing factor in the development and progression of DPN.
Methods
Data were gathered from 1211 type 2 diabetes patients admitted to five centers from September 2018 to October 2022 in China. DPN was evaluated by symptoms and electromyography. Motor and sensory nerve conduction velocity (NCV) was appraised and the NCV sum score was calculated for the median, ulnar, and peroneal motor or sensory nerves.
Results
Patients with DPN exhibited alterations in coagulation function. (i) Specifically, they exhibited prolonged thrombin time (p = 0.012), elevated fibrinogen (p < 0.001), and shortened activated partial thromboplastin time (APTT; p = 0.026) when compared to the control group. (ii) After accounting for potential confounders in linear regression, fibrinogen, and D-dimer were negatively related to the motor NCV, motor amplitude values, and mean velocity and amplitude. Also, fibrinogen was associated with higher Michigan neuropathy screening instrument (MNSI) scores (β 0.140; p = 0.001). This result of fibrinogen can be validated in the validation cohort with 317 diabetic patients. (iii) Fibrinogen was independently associated with the risk of DPN (OR 1.172; p = 0.035). In the total age group, DPN occurred at a slower rate until the predicted fibrinogen level reached around 3.75 g/L, after which the risk sharply escalated.
Conclusions
Coagulation function is warranted to be concerned in patients with type 2 diabetes to predict and prevent the occurrence of DPN in clinical practice.
{"title":"Whether coagulation dysfunction influences the onset and progression of diabetic peripheral neuropathy: A multicenter study in middle-aged and aged patients with type 2 diabetes","authors":"Jiali Xie, Xinyue Yu, Luowei Chen, Yifan Cheng, Kezheng Li, Mengwan Song, Yinuo Chen, Fei Feng, Yunlei Cai, Shuting Tong, Yuqin Qian, Yiting Xu, Haiqin Zhang, Junjie Yang, Zirui Xu, Can Cui, Huan Yu, Binbin Deng","doi":"10.1111/cns.70040","DOIUrl":"https://doi.org/10.1111/cns.70040","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nearly half of patients with diabetes experience diabetic peripheral neuropathy (DPN), resulting in a mere 53% survival rate within 3 years. Aberrations in coagulation function have been implicated in the pathogenesis of microvascular complications, prompting the need for a thorough investigation into its role as a contributing factor in the development and progression of DPN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were gathered from 1211 type 2 diabetes patients admitted to five centers from September 2018 to October 2022 in China. DPN was evaluated by symptoms and electromyography. Motor and sensory nerve conduction velocity (NCV) was appraised and the NCV sum score was calculated for the median, ulnar, and peroneal motor or sensory nerves.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with DPN exhibited alterations in coagulation function. (i) Specifically, they exhibited prolonged thrombin time (<i>p</i> = 0.012), elevated fibrinogen (<i>p</i> < 0.001), and shortened activated partial thromboplastin time (APTT; <i>p</i> = 0.026) when compared to the control group. (ii) After accounting for potential confounders in linear regression, fibrinogen, and D-dimer were negatively related to the motor NCV, motor amplitude values, and mean velocity and amplitude. Also, fibrinogen was associated with higher Michigan neuropathy screening instrument (MNSI) scores (<i>β</i> 0.140; <i>p</i> = 0.001). This result of fibrinogen can be validated in the validation cohort with 317 diabetic patients. (iii) Fibrinogen was independently associated with the risk of DPN (OR 1.172; <i>p</i> = 0.035). In the total age group, DPN occurred at a slower rate until the predicted fibrinogen level reached around 3.75 g/L, after which the risk sharply escalated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Coagulation function is warranted to be concerned in patients with type 2 diabetes to predict and prevent the occurrence of DPN in clinical practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu-Mei Yu, Rui Yao, Zhou-Liang Liu, Yao Lu, Yang-Zi Zhu, Jun-Li Cao
Aims
Transcutaneous auricular vagus nerve stimulation (taVNS) is widely used to treat a variety of disorders because it is noninvasive, safe, and well tolerated by awake patients. However, long-term and repetitive taVNS is difficult to achieve in awake mice. Therefore, developing a new taVNS method that fully mimics the method used in clinical settings and is well-tolerated by awake mice is greatly important for generalizing research findings related to the effects of taVNS. The study aimed to develop a new taVNS device for use in awake mice and to test its reliability and effectiveness.
Methods
We demonstrated the reliability of this taVNS device through retrograde neurotropic pseudorabies virus (PRV) tracing and evaluated its effectiveness through morphological analysis. After 3 weeks of taVNS application, the open field test (OFT) and elevated plus maze (EPM) were used to evaluate anxiety-like behaviors, and the Y-maze test and novel object recognition test (NORT) were used to evaluate recognition memory behaviors, respectively.
Results
We found that repetitive taVNS was well tolerated by awake mice, had no effect on anxiety-like behaviors, and significantly improved memory.
Conclusion
Our findings suggest that this new taVNS device for repetitive stimulation of awake mice is safe, tolerable, and effective.
{"title":"Feasibility and effectiveness of transcutaneous auricular vagus nerve stimulation (taVNS) in awake mice","authors":"Yu-Mei Yu, Rui Yao, Zhou-Liang Liu, Yao Lu, Yang-Zi Zhu, Jun-Li Cao","doi":"10.1111/cns.70043","DOIUrl":"https://doi.org/10.1111/cns.70043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Transcutaneous auricular vagus nerve stimulation (taVNS) is widely used to treat a variety of disorders because it is noninvasive, safe, and well tolerated by awake patients. However, long-term and repetitive taVNS is difficult to achieve in awake mice. Therefore, developing a new taVNS method that fully mimics the method used in clinical settings and is well-tolerated by awake mice is greatly important for generalizing research findings related to the effects of taVNS. The study aimed to develop a new taVNS device for use in awake mice and to test its reliability and effectiveness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We demonstrated the reliability of this taVNS device through retrograde neurotropic pseudorabies virus (PRV) tracing and evaluated its effectiveness through morphological analysis. After 3 weeks of taVNS application, the open field test (OFT) and elevated plus maze (EPM) were used to evaluate anxiety-like behaviors, and the Y-maze test and novel object recognition test (NORT) were used to evaluate recognition memory behaviors, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that repetitive taVNS was well tolerated by awake mice, had no effect on anxiety-like behaviors, and significantly improved memory.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that this new taVNS device for repetitive stimulation of awake mice is safe, tolerable, and effective.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sepsis-associated encephalopathy (SAE) is a neuronal injury with poor prognosis. Mitochondrial dysfunction is critical in SAE development, and hydrogen gas (H2) has a protective effect on septic mice. This study aimed to investigate the effect of high concentration (67%) of H2 on SAE and whether it is related to mitochondrial biogenesis and mitochondrial dynamics.
Methods
A mouse sepsis model was induced by cecal ligation and puncture. The mice inhalated 67% H2 for 1 h at 1 and 6 h post-surgery, respectively. The 7-day survival rate was recorded. Cognitive function was assessed using the Y-maze test and Morris water maze test. Serum inflammatory factors, antioxidant enzymes, as well as mitochondrial function indexes including mitochondrial membrane potential (MMP) and ATP in the hippocampal tissue were evaluated 24 h after surgery. Mitochondrial dynamic proteins (DRP1 and MFN2) and biosynthetic proteins (PGC-1α, NRF2, and TFAM) in the hippocampal tissue were detected. Moreover, the morphology of mitochondria was observed by transmission electron microscopy.
Results
Inhalation of 67% H2 improved the 7-day survival rates and recognition memory function of septic mice, alleviated brain antioxidant enzyme activity (SOD and CAT), and reduced serum proinflammatory cytokine levels. H2 inhalation also enhanced the expression of MFN2 and mitochondrial biogenesis-related factors (PGC-1α, NRF2, and TFAM) and decreased the expression of fission protein (DRP1), leading to improvement in mitochondrial function, as evidenced by MMP and ATP levels.
Conclusions
Inhalation of high concentration (67%) of H2 in septic mice improved the survival rate and reduced neuronal injury. Its mechanism might be mediated by enhancing mitochondrial biogenesis and mitochondrial dynamics.
{"title":"High-concentration hydrogen inhalation mitigates sepsis-associated encephalopathy in mice by improving mitochondrial dynamics","authors":"Yan Cui, Shuqi Meng, Nannan Zhang, Jingya Liu, Lina Zheng, Wanjie Ma, Yu Song, Zhiwei Wang, Yuehao Shen, Jianfeng Liu, Keliang Xie","doi":"10.1111/cns.70021","DOIUrl":"https://doi.org/10.1111/cns.70021","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sepsis-associated encephalopathy (SAE) is a neuronal injury with poor prognosis. Mitochondrial dysfunction is critical in SAE development, and hydrogen gas (H<sub>2</sub>) has a protective effect on septic mice. This study aimed to investigate the effect of high concentration (67%) of H<sub>2</sub> on SAE and whether it is related to mitochondrial biogenesis and mitochondrial dynamics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A mouse sepsis model was induced by cecal ligation and puncture. The mice inhalated 67% H<sub>2</sub> for 1 h at 1 and 6 h post-surgery, respectively. The 7-day survival rate was recorded. Cognitive function was assessed using the Y-maze test and Morris water maze test. Serum inflammatory factors, antioxidant enzymes, as well as mitochondrial function indexes including mitochondrial membrane potential (MMP) and ATP in the hippocampal tissue were evaluated 24 h after surgery. Mitochondrial dynamic proteins (DRP1 and MFN2) and biosynthetic proteins (PGC-1α, NRF2, and TFAM) in the hippocampal tissue were detected. Moreover, the morphology of mitochondria was observed by transmission electron microscopy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Inhalation of 67% H<sub>2</sub> improved the 7-day survival rates and recognition memory function of septic mice, alleviated brain antioxidant enzyme activity (SOD and CAT), and reduced serum proinflammatory cytokine levels. H<sub>2</sub> inhalation also enhanced the expression of MFN2 and mitochondrial biogenesis-related factors (PGC-1α, NRF2, and TFAM) and decreased the expression of fission protein (DRP1), leading to improvement in mitochondrial function, as evidenced by MMP and ATP levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Inhalation of high concentration (67%) of H<sub>2</sub> in septic mice improved the survival rate and reduced neuronal injury. Its mechanism might be mediated by enhancing mitochondrial biogenesis and mitochondrial dynamics.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shan Wei, Weng Shiwen, Chang Cao-wenjing, Yang Huajun, Wang Qun
Aims
This study aims to investigate the safety, tolerability, efficacy, and pharmacokinetics of Pynegabine as an add-on therapy in the treatment of focal epilepsy.
Methodology
This is a protocol phase-IIa, randomized, double-blinded, placebo-controlled, multicenter study in patients with focal epilepsy from multiple centers in China who have been treated with at least 2 ASMs without effective control. The study involves an 8-week run-in period with stable use of previous medications. Patients are then randomized to receive either Pynegabine or a placebo. Sentinel administration is performed initially, and subsequent patients are randomized based on safety assessments. Three dose cohorts (15, 20, and 25 mg/d) are established. Efficacy is assessed through various measures, including seizure frequency, CGI score, PGI score, HAMA score, HAMD score, MoCA scale score, QOLIE-31 scale score, and 12 h-EEG score. Safety evaluations, PK blood samples, concomitant medications, and adverse events are also recorded.
Conclusion
Data from the study will be used to evaluate the safety, tolerability, efficacy, and pharmacokinetics of Pynegabine tablets as add-on therapy for focal epilepsy.
{"title":"A randomized, double-blind, placebo-controlled, dose-escalating phase IIa trial to evaluate the safety, tolerability, efficacy, and pharmacokinetics of multiple oral doses of Pynegabine tablets as add-on therapy in patients with focal epilepsy","authors":"Shan Wei, Weng Shiwen, Chang Cao-wenjing, Yang Huajun, Wang Qun","doi":"10.1111/cns.70002","DOIUrl":"https://doi.org/10.1111/cns.70002","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aims to investigate the safety, tolerability, efficacy, and pharmacokinetics of Pynegabine as an add-on therapy in the treatment of focal epilepsy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>This is a protocol phase-IIa, randomized, double-blinded, placebo-controlled, multicenter study in patients with focal epilepsy from multiple centers in China who have been treated with at least 2 ASMs without effective control. The study involves an 8-week run-in period with stable use of previous medications. Patients are then randomized to receive either Pynegabine or a placebo. Sentinel administration is performed initially, and subsequent patients are randomized based on safety assessments. Three dose cohorts (15, 20, and 25 mg/d) are established. Efficacy is assessed through various measures, including seizure frequency, CGI score, PGI score, HAMA score, HAMD score, MoCA scale score, QOLIE-31 scale score, and 12 h-EEG score. Safety evaluations, PK blood samples, concomitant medications, and adverse events are also recorded.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Data from the study will be used to evaluate the safety, tolerability, efficacy, and pharmacokinetics of Pynegabine tablets as add-on therapy for focal epilepsy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nowadays, the prevalence of cognitive impairment in women has gradually increased, especially in postmenopausal women. There were few studies on the mechanistic effects of iron exposure on neurotoxicity in postmenopausal women. The aim of this study is to investigate the effect of iron accumulation on cognitive ability in ovariectomized mice and its possible mechanism and to provide a scientific basis for the prevention of cognitive dysfunction in postmenopausal women.
Methods
Female C57BL/6N ovariectomized model mice were induced with ferric citrate (FAC). The mice were randomly divided into 5 groups: control, sham, ovariectomized (Ovx), Ovx + 50 mg/kg FAC (Ovx + l), and Ovx + 100 mg/kg FAC (Ovx + h). The impact of motor and cognitive function was verified by a series of behavioral tests. The levels of serum iron parameters, malondialdehyde, and superoxide dismutase were measured. The ultrastructure of mice hippocampal microglia was imaged by transmission electron microscopy. The differential expression of hippocampal proteins was analyzed by Tandem Mass Tag labeling.
Results
Movement and cognitive function in Ovx + l/Ovx + h mice were significantly decreased compared to control and Sham mice. Then, iron exposure caused histopathological changes in the hippocampus of mice. In addition, proteomic analysis revealed that 29/27/41 proteins were differentially expressed in the hippocampus when compared by Ovx vs. Sham, Ovx + l vs. Ovx, as well as Ovx + h vs. Ovx + l groups, respectively. Moreover, transferrin receptor protein (TFR1) and divalent metal transporter 1 (DMT1) protein expression were significantly increased in the iron accumulation mice model with ovariectomy.
Conclusion
Iron exposure could cause histopathological damage in the hippocampus of ovariectomised mice and, by altering hippocampal proteomics, particularly the expression of hippocampal iron metabolism-related proteins, could further influence cognitive impairment in ovariectomized mice.
{"title":"Effect of ferric citrate on hippocampal iron accumulation and widespread molecular alterations associated with cognitive disorder in an ovariectomized mice model","authors":"Lingling Cui, Huijun Zhou, Yudan Hao, Xiaoli Yang, Zhiqian Li, Yuting Gao, Zhengya Zhang, Lina Ren, Linpu Ji, Ruijie Sun, Yibo Wang, Xian Wang","doi":"10.1111/cns.70018","DOIUrl":"https://doi.org/10.1111/cns.70018","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Nowadays, the prevalence of cognitive impairment in women has gradually increased, especially in postmenopausal women. There were few studies on the mechanistic effects of iron exposure on neurotoxicity in postmenopausal women. The aim of this study is to investigate the effect of iron accumulation on cognitive ability in ovariectomized mice and its possible mechanism and to provide a scientific basis for the prevention of cognitive dysfunction in postmenopausal women.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Female C57BL/6N ovariectomized model mice were induced with ferric citrate (FAC). The mice were randomly divided into 5 groups: control, sham, ovariectomized (Ovx), Ovx + 50 mg/kg FAC (Ovx + l), and Ovx + 100 mg/kg FAC (Ovx + h). The impact of motor and cognitive function was verified by a series of behavioral tests. The levels of serum iron parameters, malondialdehyde, and superoxide dismutase were measured. The ultrastructure of mice hippocampal microglia was imaged by transmission electron microscopy. The differential expression of hippocampal proteins was analyzed by Tandem Mass Tag labeling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Movement and cognitive function in Ovx + l/Ovx + h mice were significantly decreased compared to control and Sham mice. Then, iron exposure caused histopathological changes in the hippocampus of mice. In addition, proteomic analysis revealed that 29/27/41 proteins were differentially expressed in the hippocampus when compared by Ovx vs. Sham, Ovx + l vs. Ovx, as well as Ovx + h vs. Ovx + l groups, respectively. Moreover, transferrin receptor protein (TFR1) and divalent metal transporter 1 (DMT1) protein expression were significantly increased in the iron accumulation mice model with ovariectomy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Iron exposure could cause histopathological damage in the hippocampus of ovariectomised mice and, by altering hippocampal proteomics, particularly the expression of hippocampal iron metabolism-related proteins, could further influence cognitive impairment in ovariectomized mice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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