Neuroscience Letters最新文献_第9页

Relationship between prefrontal oxygenation during task-set period and executive function in healthy older people: A near-infrared spectroscopy study 健康老年人任务设定期前额叶氧合与执行功能的关系：近红外光谱研究

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-09-27 DOI: 10.1016/j.neulet.2025.138395

Yumi Oboshi , Mitsuru Kikuchi , Yasuomi Ouchi

Introduction

In past research, we have examined the characteristics of brain activity caused by prefrontal task completion in healthy older adults in a simplified manner using a near-infrared spectroscopy device, with the aim of identifying methods of early intervention to prevent their cognitive decline. Previously, we reported that prefrontal oxygenation during pre-task preparation was greater in young adults than older adults, and that this greater activation was associated with better task performances in both groups. To extend this research, in the present study, we examined previous findings with task repetitions, as older adults take more time to become familiar new tasks.

Methods

We modified the working memory task with a clear task-set instruction and examined the change in the task-set and task-induced activation in 63 cognitively healthy older adults.

Results

Task-set activation did not increase even after three repetitions, and the task-induced activation was greater than task-set activation in most channels. The difference in degree between task-induced activation and task-set activation showed a reduction with task repetitions. Significant inverse correlations were observed between the prefrontal activation due to the task itself in the third session, i.e., after task repetitions and the reaction time of the Trail Making Test, which represents attentional function.

Discussion

These results indicate that continued activation by the task itself, which persists even after older adults become familiar with the task, may be associated with executive function decline.

在过去的研究中，我们使用近红外光谱设备以简化的方式检查了健康老年人前额叶任务完成引起的大脑活动特征，目的是确定早期干预方法，以防止他们的认知能力下降。在此之前，我们报道了年轻人在任务前准备过程中的前额叶氧合比老年人更大，并且这种更大的激活与两组更好的任务表现有关。为了扩展这项研究，在本研究中，我们对先前的研究结果进行了检查，因为老年人需要更多的时间来熟悉新任务。方法：采用明确的任务集指令修改工作记忆任务，观察63名认知健康老年人工作记忆任务集和任务诱发激活的变化。结果：三次重复后，任务集激活并未增加，且大多数通道的任务诱发激活大于任务集激活。任务诱发激活和任务集激活的程度差异随着任务的重复而减小。在第三阶段，即任务重复后，由任务本身引起的前额叶激活与代表注意功能的造径测试反应时间呈显著负相关。讨论：这些结果表明，任务本身的持续激活，即使在成年人熟悉任务后仍然存在，可能与执行功能下降有关。

{"title":"Relationship between prefrontal oxygenation during task-set period and executive function in healthy older people: A near-infrared spectroscopy study","authors":"Yumi Oboshi , Mitsuru Kikuchi , Yasuomi Ouchi","doi":"10.1016/j.neulet.2025.138395","DOIUrl":"10.1016/j.neulet.2025.138395","url":null,"abstract":"<div><h3>Introduction</h3><div>In past research, we have examined the characteristics of brain activity caused by prefrontal task completion in healthy older adults in a simplified manner using a near-infrared spectroscopy device, with the aim of identifying methods of early intervention to prevent their cognitive decline. Previously, we reported that prefrontal oxygenation during pre-task preparation was greater in young adults than older adults, and that this greater activation was associated with better task performances in both groups. To extend this research, in the present study, we examined previous findings with task repetitions, as older adults take more time to become familiar new tasks.</div></div><div><h3>Methods</h3><div>We modified the working memory task with a clear task-set instruction and examined the change in the task-set and task-induced activation in 63 cognitively healthy older adults.</div></div><div><h3>Results</h3><div>Task-set activation did not increase even after three repetitions, and the task-induced activation was greater than task-set activation in most channels. The difference in degree between task-induced activation and task-set activation showed a reduction with task repetitions. Significant inverse correlations were observed between the prefrontal activation due to the task itself in the third session, i.e., after task repetitions and the reaction time of the Trail Making Test, which represents attentional function.</div></div><div><h3>Discussion</h3><div>These results indicate that continued activation by the task itself, which persists even after older adults become familiar with the task, may be associated with executive function decline.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"868 ","pages":"Article 138395"},"PeriodicalIF":2.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nicotine exacerbates fear and depression-like behaviors by promoting microglial phagocytosis of synaptic protein in a mouse model of foot shock 在足震小鼠模型中，尼古丁通过促进突触蛋白的小胶质吞噬而加剧恐惧和抑郁样行为。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-09-25 DOI: 10.1016/j.neulet.2025.138394

Jiaquan Wang , Xiao-kang Gong , Jing Yu , Liangwei Wu , Yuheng Zhang , Pan Li , Min Qin , Xiao-chuan Wang , Xi-ji Shu , Jian Bao

Post-traumatic stress disorder (PTSD) is a severe psychiatric disorder characterized by a complex interplay of genetic and environmental influences. Substantial evidence has demonstrated an intricate nexus between nicotine, the principal psychoactive constituent of cigarette smoke, and PTSD neuropathology. Nevertheless, the intricate mechanism underlying the relationship between nicotine consumption and PTSD has not yet been fully understood. Following two weeks of intraperitoneal nicotine administration at two doses (5 mg/kg and 1 mg/kg), we initiated behavioral testing. Our findings reveal that nicotine supplementation exacerbates fear and depression-like behaviors while promoting microglial phagocytosis of synaptic proteins. Moreover, we observed synaptic protein loss and microglial activation in both the hippocampus and cortex in the 5 mg/kg group. CX3CR1-Cre driven Cre recombinase (Cre) is a widely used genetic tool for enabling gene manipulation in microglia. Here, we investigated a genetic ablation method of the CX3CR1 using a Cre-responsive adeno-associated virus (AAV) vector expressing diphtheria toxin subunit-A (DTA). Conversely, microglial ablation via rAAV-EF1a-DIO-DTA-WPRE hGH pA injection in the ventral hippocampus CA1 region of CX3CR1-Cre mice appears to mitigate the pathologies and behavioral abnormalities induced by nicotine. Our results underscore the role of nicotine in the progression of PTSD and demonstrate that microglial depletion mitigates nicotine-induced pathologies and behavioral disturbances. Consequently, our findings suggest that nicotine enhances microglial phagocytosis of synaptic proteins in PTSD, thereby exacerbating fear and depressive symptoms.

创伤后应激障碍（PTSD）是一种严重的精神障碍，其特征是遗传和环境影响的复杂相互作用。大量证据表明尼古丁（香烟烟雾的主要精神活性成分）与创伤后应激障碍神经病理学之间存在复杂的联系。然而，尼古丁摄入和创伤后应激障碍之间关系的复杂机制尚不完全清楚。在两周的两种剂量（5 mg/kg和1 mg/kg）的尼古丁腹腔注射后，我们开始了行为测试。我们的研究结果表明，尼古丁补充加剧了恐惧和抑郁样行为，同时促进突触蛋白的小胶质吞噬。此外，我们观察到5 mg/kg组海马和皮质突触蛋白丢失和小胶质细胞激活。CX3CR1-Cre驱动的Cre重组酶（Cre）是一种广泛使用的基因工具，可以在小胶质细胞中进行基因操作。本研究利用表达白喉毒素亚单位-a （DTA）的cree应答腺相关病毒（AAV）载体研究了CX3CR1基因消融方法。相反，通过注射rAAV-EF1a-DIO-DTA-WPRE - hGH pA在CX3CR1-Cre小鼠腹侧海马CA1区消融小胶质细胞似乎可以减轻尼古丁诱导的病理和行为异常。我们的研究结果强调了尼古丁在创伤后应激障碍进展中的作用，并证明小胶质细胞耗竭减轻了尼古丁引起的病理和行为障碍。因此，我们的研究结果表明，尼古丁增强了创伤后应激障碍突触蛋白的小胶质吞噬，从而加剧了恐惧和抑郁症状。

{"title":"Nicotine exacerbates fear and depression-like behaviors by promoting microglial phagocytosis of synaptic protein in a mouse model of foot shock","authors":"Jiaquan Wang , Xiao-kang Gong , Jing Yu , Liangwei Wu , Yuheng Zhang , Pan Li , Min Qin , Xiao-chuan Wang , Xi-ji Shu , Jian Bao","doi":"10.1016/j.neulet.2025.138394","DOIUrl":"10.1016/j.neulet.2025.138394","url":null,"abstract":"<div><div>Post-traumatic stress disorder (PTSD) is a severe psychiatric disorder characterized by a complex interplay of genetic and environmental influences. Substantial evidence has demonstrated an intricate nexus between nicotine, the principal psychoactive constituent of cigarette smoke, and PTSD neuropathology. Nevertheless, the intricate mechanism underlying the relationship between nicotine consumption and PTSD has not yet been fully understood. Following two weeks of intraperitoneal nicotine administration at two doses (5 mg/kg and 1 mg/kg), we initiated behavioral testing. Our findings reveal that nicotine supplementation exacerbates fear and depression-like behaviors while promoting microglial phagocytosis of synaptic proteins. Moreover, we observed synaptic protein loss and microglial activation in both the hippocampus and cortex in the 5 mg/kg group. CX3CR1-Cre driven Cre recombinase (Cre) is a widely used genetic tool for enabling gene manipulation in microglia. Here, we investigated a genetic ablation method of the CX3CR1 using a Cre-responsive adeno-associated virus (AAV) vector expressing diphtheria toxin subunit-A (DTA). Conversely, microglial ablation via rAAV-EF1a-DIO-DTA-WPRE hGH pA injection in the ventral hippocampus CA1 region of CX3CR1-Cre mice appears to mitigate the pathologies and behavioral abnormalities induced by nicotine. Our results underscore the role of nicotine in the progression of PTSD and demonstrate that microglial depletion mitigates nicotine-induced pathologies and behavioral disturbances. Consequently, our findings suggest that nicotine enhances microglial phagocytosis of synaptic proteins in PTSD, thereby exacerbating fear and depressive symptoms.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"867 ","pages":"Article 138394"},"PeriodicalIF":2.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Short-term effects of sertraline against depressive-like behaviors in a rat model of neonatal hypoxic encephalopathy 舍曲林对新生儿缺氧脑病大鼠模型抑郁样行为的短期影响。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-09-24 DOI: 10.1016/j.neulet.2025.138392

Marie-Michèle Serghani , Sondos Kassem-Moussa , Rawan Makki , Abdallah Kurdi , Marawan Elbaset , Helene Hajjar , Reem El Jammal , Gabriel T. Flath-Everhard , Ishaan Prasad , Assaad Eid , Aida Habib , Eva Hamade , Fletcher A. White , Bassam Badran , Makram Obeid

Hypoxic encephalopathy of the newborn is associated with long-term neurodevelopmental behavioral deficits that lack a definitive “optimal” treatment approach. We previously demonstrated that periadolescent depressive-like behaviors occur in a rat model of early-life hypoxia. Here, we investigated the short-term effects of the selective serotonin reuptake inhibitor, sertraline, against later-life behavioral deficits. Rats were exposed to global hypoxia at postnatal day 10 (P10) and then received either sertraline or its vehicle (P24 to P30). Normoxic controls received sertraline or its vehicle. Depressive-like and anxiety-like behaviors were assessed using the forced swim test (FST) and open field test (OFT), respectively. The FST was conducted at P25-26 and the OFT at P27. Rats were sacrificed at P30 to assess hippocampal microRNA (miR) expression and to histologically evaluate hippocampal neuronal densities and synaptophysin (Syp) protein levels. Early-life hypoxic seizures resulted in increased immobility in the FST (p < 0.05) and decreased exploration in the OFT (p < 0.05). Hypoxia also resulted in chronic alterations in the expression of 25 miRs, 22 of which are known to modulate inflammatory responses and synaptic function. Sertraline treatment normalized hypoxia-induced increased immobility and reversed 17 out of 25 alterations in miR expression. However, sertraline potentiated hypoxia-induced exploratory deficits (p < 0.05). The drug treatment also resulted in OFT deficits in controls (p < 0.05) and 13 unique dysregulations in miR expression. Neuronal densities and Syp levels were comparable among all groups. We demonstrate that sertraline reverses hypoxia-induced depressive-like behaviors, possibly by targeting inflammation and synaptic remodeling. Sertraline-induced anxiety-like behaviors may reflect its known transient early side effects and warrant further research on long-term outcomes.

新生儿缺氧脑病与长期神经发育行为缺陷有关，缺乏明确的“最佳”治疗方法。我们之前证明了青春期周围类似抑郁的行为发生在早期缺氧的大鼠模型中。在这里，我们研究了选择性血清素再摄取抑制剂舍曲林对晚年行为缺陷的短期影响。大鼠在出生后第10天（P10）暴露于全身缺氧，然后给予舍曲林或其对照物（P24至P30）。正常对照组给予舍曲林或其载体。抑郁样行为和焦虑样行为分别采用强迫游泳测试（FST）和开放场测试（OFT）进行评估。FST在P25-26处进行，OFT在P27处进行。在P30时处死大鼠，以评估海马microRNA （miR）表达，组织学上评估海马神经元密度和突触素（Syp）蛋白水平。早期缺氧发作导致FST不活动增加(p

{"title":"Short-term effects of sertraline against depressive-like behaviors in a rat model of neonatal hypoxic encephalopathy","authors":"Marie-Michèle Serghani , Sondos Kassem-Moussa , Rawan Makki , Abdallah Kurdi , Marawan Elbaset , Helene Hajjar , Reem El Jammal , Gabriel T. Flath-Everhard , Ishaan Prasad , Assaad Eid , Aida Habib , Eva Hamade , Fletcher A. White , Bassam Badran , Makram Obeid","doi":"10.1016/j.neulet.2025.138392","DOIUrl":"10.1016/j.neulet.2025.138392","url":null,"abstract":"<div><div>Hypoxic encephalopathy of the newborn is associated with long-term neurodevelopmental behavioral deficits that lack a definitive “optimal” treatment approach. We previously demonstrated that periadolescent depressive-like behaviors occur in a rat model of early-life hypoxia. Here, we investigated the short-term effects of the selective serotonin reuptake inhibitor, sertraline, against later-life behavioral deficits. Rats were exposed to global hypoxia at postnatal day 10 (P10) and then received either sertraline or its vehicle (P24 to P30). Normoxic controls received sertraline or its vehicle. Depressive-like and anxiety-like behaviors were assessed using the forced swim test (FST) and open field test (OFT), respectively. The FST was conducted at P25-26 and the OFT at P27. Rats were sacrificed at P30 to assess hippocampal microRNA (miR) expression and to histologically evaluate hippocampal neuronal densities and synaptophysin (Syp) protein levels. Early-life hypoxic seizures resulted in increased immobility in the FST (p < 0.05) and decreased exploration in the OFT (p < 0.05). Hypoxia also resulted in chronic alterations in the expression of 25 miRs, 22 of which are known to modulate inflammatory responses and synaptic function. Sertraline treatment normalized hypoxia-induced increased immobility and reversed 17 out of 25 alterations in miR expression. However, sertraline potentiated hypoxia-induced exploratory deficits (p < 0.05). The drug treatment also resulted in OFT deficits in controls (p < 0.05) and 13 unique dysregulations in miR expression. Neuronal densities and Syp levels were comparable among all groups. We demonstrate that sertraline reverses hypoxia-induced depressive-like behaviors, possibly by targeting inflammation and synaptic remodeling. Sertraline-induced anxiety-like behaviors may reflect its known transient early side effects and warrant further research on long-term outcomes.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"867 ","pages":"Article 138392"},"PeriodicalIF":2.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Blockade of acid-sensing ion channels 1a in the mice dorsal raphe nucleus inhibits panic-like responses: Role of 5-HT1A receptors in the dorsal periaqueductal gray 阻断小鼠中缝背核酸敏感离子通道1a抑制恐慌样反应：5-HT1A受体在背侧导水管周围灰质中的作用

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-09-22 DOI: 10.1016/j.neulet.2025.138389

Alana Tercino Frias, Paloma Molina Hernandes, Helio Zangrossi Jr

Panic attacks, characterized by intense fear accompanied by autonomic and respiratory changes, can be experimentally modeled in humans and rodents by exposure to high concentrations of CO₂. Acid-sensing ion channels (ASICs), particularly the ASIC1a subtype, are activated by decrease in pH and have been implicated in defensive responses triggered by hypercapnia. ASIC1a are found in key panic-associated areas such as the lateral wings of the dorsal raphe nucleus (lwDRN) and the dorsal periaqueductal gray (dPAG). Here, we first investigated whether ASIC1a channels in the lwDRN modulate the expression of panic-associated escape response in mice. C57BL/6 mice received intra-lwDRN injections of psalmotoxin-1 (Pstx-1; 12.5 or 25 ηg/50 ηL), a selective ASIC1a blocker, and were exposed to 20% CO₂. ASIC1a blockade significantly reduced escape behavior without affecting baseline locomotion, suggesting a panicolytic-like effect. This effect was site-specific and abolished by intra-dPAG administration of WAY100635 (0.74 ηmol/50 ηL), a 5-HT_1A receptor antagonist. Our study provides novel evidence that ASIC1a channels in the lwDRN contribute to CO₂-evoked escape responses and that this modulation depends on serotonergic signaling via 5-HT_1A receptors in the dPAG. These findings offer new insights into the neurobiology of panic attacks paving the way for the development of more precise treatments for PD.

惊恐发作的特征是强烈的恐惧，并伴有自主神经和呼吸系统的变化，可以通过暴露于高浓度的二氧化碳在人类和啮齿动物身上进行实验模拟。酸敏感离子通道（asic），特别是ASIC1a亚型，可被pH降低激活，并与高碳酸血症引发的防御反应有关。ASIC1a存在于关键的恐慌相关区域，如中缝背核侧翼（lwDRN）和背侧导水管周围灰质（dPAG）。在这里，我们首先研究了lwDRN中的ASIC1a通道是否调节小鼠恐慌相关逃避反应的表达。C57BL/6小鼠在lwdrn内注射选择性ASIC1a阻断剂- Pstx-1 (Pstx-1； 12.5或25 ηg/50 ηL)，并暴露于20%的CO2中。ASIC1a阻断显著减少了逃跑行为，而不影响基线运动，提示类似于恐慌的作用。这种作用是位点特异性的，并通过在dpag内给予WAY100635 (0.74 ηmol/50 ηL)（一种5-HT1A受体拮抗剂）来消除。我们的研究提供了新的证据，证明lwDRN中的ASIC1a通道有助于二氧化碳诱发的逃逸反应，并且这种调节依赖于dPAG中5-HT1A受体的血清素能信号传导。这些发现为惊恐发作的神经生物学提供了新的见解，为开发更精确的PD治疗方法铺平了道路。

{"title":"Blockade of acid-sensing ion channels 1a in the mice dorsal raphe nucleus inhibits panic-like responses: Role of 5-HT1A receptors in the dorsal periaqueductal gray","authors":"Alana Tercino Frias, Paloma Molina Hernandes, Helio Zangrossi Jr","doi":"10.1016/j.neulet.2025.138389","DOIUrl":"10.1016/j.neulet.2025.138389","url":null,"abstract":"<div><div>Panic attacks, characterized by intense fear accompanied by autonomic and respiratory changes, can be experimentally modeled in humans and rodents by exposure to high concentrations of CO<sub>2</sub>. Acid-sensing ion channels (ASICs), particularly the ASIC1a subtype, are activated by decrease in pH and have been implicated in defensive responses triggered by hypercapnia. ASIC1a are found in key panic-associated areas such as the lateral wings of the dorsal raphe nucleus (lwDRN) and the dorsal periaqueductal gray (dPAG). Here, we first investigated whether ASIC1a channels in the lwDRN modulate the expression of panic-associated escape response in mice. C57BL/6 mice received intra-lwDRN injections of psalmotoxin-1 (Pstx-1; 12.5 or 25 ηg/50 ηL), a selective ASIC1a blocker, and were exposed to 20% CO<sub>2</sub>. ASIC1a blockade significantly reduced escape behavior without affecting baseline locomotion, suggesting a panicolytic-like effect. This effect was site-specific and abolished by intra-dPAG administration of WAY100635 (0.74 ηmol/50 ηL), a 5-HT<sub>1A</sub> receptor antagonist. Our study provides novel evidence that ASIC1a channels in the lwDRN contribute to CO<sub>2</sub>-evoked escape responses and that this modulation depends on serotonergic signaling via 5-HT<sub>1A</sub> receptors in the dPAG. These findings offer new insights into the neurobiology of panic attacks paving the way for the development of more precise treatments for PD.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"867 ","pages":"Article 138389"},"PeriodicalIF":2.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tanshinone IIA and hydroxy safflower yellow A reduce cerebral injury via TLR4/NF-κB pathway in rats 丹参酮IIA和羟基红花黄A通过TLR4/NF-κB通路减轻大鼠脑损伤。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-09-22 DOI: 10.1016/j.neulet.2025.138390

Bin Luo , Yu Zheng , Qi Miao , Yimin Zhang , Ye Lei , Qingyun Xu , Wenwu Li , Jingao Yu , Xiao Zhu , Jianlin Yuan , Huiyuan Zhu

Cerebral ischemia–reperfusion injury (CIRI) is a cerebrovascular disorder with high rates of incidence, disability, and death. It has been identified that Salvia miltiorrhiza and safflower have a protective effect in CIRI. However, the mechanisms of which remain to be elucidated. In this study, we investigated the protective mechanisms of the components of Salvia miltiorrhiza and safflower in CIRI, based on the TLR4/NF-κB signaling pathway. Sprague Dawley (SD) rats were used to establish the rat middle cerebral artery occlusion/reperfusion (MACO/R) model by the suture method. Drugs were injected intraperitoneally at 0 and 2 h, followed by once-daily treatment for 3 days. Neurological function and the volume of brain infarction were evaluated, and the pathological changes in brain tissue were examined using HE staining. ELISA kits were used to detect the concentrations of TNF-α and IL-6, while RT-qPCR, Western blot, and immunofluorescence were employed to evaluate the mRNA and protein expression in brain tissue. Following a combination of tanshinone IIA and hydroxy safflower yellow A treatment, our findings indicated that cerebral infarct volume and neurological deficits were reduced. The findings of HE staining revealed an improvement in cerebral histopathological damage in rats with MCAO/R. The levels of TNF-α and IL-6 in serum, as well as the expression of TLR4 and NF-κB in rat brains, were significantly reduced (P < 0.0001). Taken together, these results indicate that the combination of tanshinone ⅡA and hydroxyl safflower yellow A may exhibit a neuroprotective effect on cerebral I/R injury in rats by activating the TLR4/NF-κB signaling pathway.

脑缺血再灌注损伤（CIRI）是一种发病率高、致残率高、死亡率高的脑血管疾病。丹参和红花对CIRI有一定的保护作用。然而，其机制仍有待阐明。本研究基于TLR4/NF-κB信号通路，探讨丹参和红花成分对CIRI的保护作用机制。采用spague Dawley （SD）大鼠缝合法建立大鼠大脑中动脉闭塞/再灌注（MACO/R）模型。分别于0、2 h腹腔注射药物，每日1次，连用3 d。观察大鼠神经功能及脑梗死体积，HE染色观察脑组织病理变化。采用ELISA试剂盒检测TNF-α、IL-6浓度，RT-qPCR、Western blot、免疫荧光法检测脑组织mRNA和蛋白表达。在丹参酮IIA和羟基红花黄a联合治疗后，我们的研究结果表明脑梗死体积和神经功能缺损减少。HE染色结果显示MCAO/R大鼠脑组织病理学损伤得到改善。大鼠血清中TNF-α、IL-6水平及脑组织中TLR4、NF-κB表达均显著降低(P

{"title":"Tanshinone IIA and hydroxy safflower yellow A reduce cerebral injury via TLR4/NF-κB pathway in rats","authors":"Bin Luo , Yu Zheng , Qi Miao , Yimin Zhang , Ye Lei , Qingyun Xu , Wenwu Li , Jingao Yu , Xiao Zhu , Jianlin Yuan , Huiyuan Zhu","doi":"10.1016/j.neulet.2025.138390","DOIUrl":"10.1016/j.neulet.2025.138390","url":null,"abstract":"<div><div>Cerebral ischemia–reperfusion injury (CIRI) is a cerebrovascular disorder with high rates of incidence, disability, and death. It has been identified that Salvia miltiorrhiza and safflower have a protective effect in CIRI. However, the mechanisms of which remain to be elucidated. In this study, we investigated the protective mechanisms of the components of Salvia miltiorrhiza and safflower in CIRI, based on the TLR4/NF-κB signaling pathway. Sprague Dawley (SD) rats were used to establish the rat middle cerebral artery occlusion/reperfusion (MACO/R) model by the suture method. Drugs were injected intraperitoneally at 0 and 2 h, followed by once-daily treatment for 3 days. Neurological function and the volume of brain infarction were evaluated, and the pathological changes in brain tissue were examined using HE staining. ELISA kits were used to detect the concentrations of TNF-α and IL-6, while RT-qPCR, Western blot, and immunofluorescence were employed to evaluate the mRNA and protein expression in brain tissue. Following a combination of tanshinone IIA and hydroxy safflower yellow A treatment, our findings indicated that cerebral infarct volume and neurological deficits were reduced. The findings of HE staining revealed an improvement in cerebral histopathological damage in rats with MCAO/R. The levels of TNF-α and IL-6 in serum, as well as the expression of TLR4 and NF-κB in rat brains, were significantly reduced (P < 0.0001). Taken together, these results indicate that the combination of tanshinone ⅡA and hydroxyl safflower yellow A may exhibit a neuroprotective effect on cerebral I/R injury in rats by activating the TLR4/NF-κB signaling pathway.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"867 ","pages":"Article 138390"},"PeriodicalIF":2.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vitamin D3 alleviates AD-like pathology in APP/PS1 mice by inhibiting pyroptosis and neuroinflammation via DJ-1/PARK7 维生素D3通过DJ-1/PARK7抑制焦亡和神经炎症，减轻APP/PS1小鼠ad样病理。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-09-21 DOI: 10.1016/j.neulet.2025.138385

Chunyu Zhou , Yulin Wang , Longfei Zuo , Yufan Miao , Wenjie Li , Xing Li , Yuan Xue , Mengxin Li

Alzheimer’s disease (AD) is the most common primary progressive neurodegenerative disorder, with inflammatory responses involved in its onset and progression. Vitamin D (VD) is known for its health benefits, including antioxidant effects. Recently, Deglycase protein 1 (DJ-1/PARK7) has been shown to potentially regulate in antioxidant activity and inflammation regulation. In this study, we investigated the therapeutic effects of VD₃ (30 IU/g/w) in Dj-1 knockdown APPswe/PS1E9 (APP/PS1) mice. Pathological changes were assessed using the Morris water maze and Barnes maze, as well as immunofluorescence, thioflavin S staining, Nissl staining, TUNEL staining, Western blot, and RT-PCR. The results demonstrated that VD₃ significantly ameliorated cognitive deficits and attenuated AD-like pathology in APP/PS1 mice. Moreover, VD₃ upregulated DJ-1 expression and suppressed neuroinflammation and neuronal pyroptosis by modulating the NF-κB/NLRP3/caspase-1 and caspase-3/GSDME signaling pathways. Collectively, these findings suggest that DJ-1 mediate these protective effects, as its knockdown reversed VD₃-induced improvements in neuroinflammation and neuronal pyroptosis, implicating that DJ-1 is a crucial modulator in the effects of VD₃ on Alzheimer’s disease pathology.

阿尔茨海默病（AD）是最常见的原发性进行性神经退行性疾病，炎症反应参与其发病和进展。维生素D （VD）因其健康益处而闻名，包括抗氧化作用。最近，脱糖苷蛋白1 （DJ-1/PARK7）已被证明在抗氧化活性和炎症调节中具有潜在的调节作用。在本研究中，我们研究了VD3（30 IU/g/w）对Dj-1敲低的APP/ PS1E9 （APP/PS1）小鼠的治疗作用。采用Morris水迷宫、Barnes迷宫、免疫荧光、硫黄素S染色、Nissl染色、TUNEL染色、Western blot、RT-PCR评估病理变化。结果表明，VD3可显著改善APP/PS1小鼠的认知缺陷和ad样病理。此外，VD3通过调节NF-κB/NLRP3/caspase-1和caspase-3/GSDME信号通路上调DJ-1表达，抑制神经炎症和神经元焦亡。总的来说，这些发现表明DJ-1介导了这些保护作用，因为它的敲除逆转了VD3诱导的神经炎症和神经元焦亡的改善，这表明DJ-1是VD3对阿尔茨海默病病理影响的关键调节剂。

{"title":"Vitamin D3 alleviates AD-like pathology in APP/PS1 mice by inhibiting pyroptosis and neuroinflammation via DJ-1/PARK7","authors":"Chunyu Zhou , Yulin Wang , Longfei Zuo , Yufan Miao , Wenjie Li , Xing Li , Yuan Xue , Mengxin Li","doi":"10.1016/j.neulet.2025.138385","DOIUrl":"10.1016/j.neulet.2025.138385","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is the most common primary progressive neurodegenerative disorder, with inflammatory responses involved in its onset and progression. Vitamin D (VD) is known for its health benefits, including antioxidant effects. Recently, Deglycase protein 1 (DJ-1/<em>PARK7</em>) has been shown to potentially regulate in antioxidant activity and inflammation regulation. In this study, we investigated the therapeutic effects of VD<sub>3</sub> (30 IU/g/w) in <em>Dj-1</em> knockdown APPswe/PS1E9 (APP/PS1) mice. Pathological changes were assessed using the Morris water maze and Barnes maze, as well as immunofluorescence, thioflavin S staining, Nissl staining, TUNEL staining, Western blot, and RT-PCR. The results demonstrated that VD<sub>3</sub> significantly ameliorated cognitive deficits and attenuated AD-like pathology in APP/PS1 mice. Moreover, VD<sub>3</sub> upregulated DJ-1 expression and suppressed neuroinflammation and neuronal pyroptosis by modulating the NF-κB/NLRP3/caspase-1 and caspase-3/GSDME signaling pathways. Collectively, these findings suggest that DJ-1 mediate these protective effects, as its knockdown reversed VD<sub>3</sub>-induced improvements in neuroinflammation and neuronal pyroptosis, implicating that DJ-1 is a crucial modulator in the effects of VD<sub>3</sub> on Alzheimer’s disease pathology.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"867 ","pages":"Article 138385"},"PeriodicalIF":2.0,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mini-Review: Cathodal tDCS over the right prefrontal cortex and inhibitory control: Pinpointing an electrode montage to disrupt a domain-general system 迷你评论：在右侧前额叶皮层和抑制控制上的阴极tDCS：精确定位电极蒙太奇来破坏域一般系统。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-09-21 DOI: 10.1016/j.neulet.2025.138388

Carlos J. Gómez-Ariza , Javier Pacios

While many tDCS studies have focused on enhancing inhibitory control, only a few have employed tDCS to disrupt the neural activity of specific brain regions and gain understanding of their contribution to inhibitory control. This mini-review describes and discusses the results of studies that specifically applied cathodal tDCS over the right dorsolateral prefrontal cortex. The majority of these studies employed variants of experimental procedures that assessed the ability to inhibit either inappropriate motor responses or competing memories during selective retrieval. In both domains, action stopping and memory downregulation, neuroimaging research has shown that successful inhibitory control engages common areas within the right lateral prefrontal cortex. Strikingly, although a significant proportion of the reviewed studies reported behavioral effects that can be interpreted as a consequence of hindering inhibitory control, they have not been previously considered or discussed altogether despite its theoretical and methodological implications. This consistent disruptive effect challenges the common belief that cathodal tDCS is ineffective in modulating performance when applied to prefrontal regions. Additionally, the results provide causal evidence that supports the proposed role of the right lateral prefrontal cortex in a domain-general inhibitory system, particularly in relation to stopping actions and downregulating competing memories.

虽然许多tDCS研究的重点是增强抑制控制，但只有少数研究使用tDCS来破坏特定大脑区域的神经活动，并了解它们对抑制控制的贡献。这篇小型综述描述并讨论了在右背外侧前额皮质上应用阴极tDCS的研究结果。这些研究大多采用不同的实验程序来评估选择性检索过程中抑制不适当运动反应或竞争性记忆的能力。在动作停止和记忆下调这两个领域，神经成像研究表明，成功的抑制性控制涉及右侧前额叶皮层的共同区域。引人注目的是，尽管这些研究中有很大一部分报告了可以解释为阻碍抑制控制的结果的行为影响，但尽管其理论和方法意义重大，但它们之前没有被考虑或讨论过。这种一致的破坏性效应挑战了人们普遍认为的阴极tDCS在前额叶区域的调制性能是无效的。此外，研究结果提供了因果证据，支持右侧前额叶皮层在域一般抑制系统中的作用，特别是在停止行为和下调竞争性记忆方面。

{"title":"Mini-Review: Cathodal tDCS over the right prefrontal cortex and inhibitory control: Pinpointing an electrode montage to disrupt a domain-general system","authors":"Carlos J. Gómez-Ariza , Javier Pacios","doi":"10.1016/j.neulet.2025.138388","DOIUrl":"10.1016/j.neulet.2025.138388","url":null,"abstract":"<div><div>While many tDCS studies have focused on enhancing inhibitory control, only a few have employed tDCS to disrupt the neural activity of specific brain regions and gain understanding of their contribution to inhibitory control. This mini-review describes and discusses the results of studies that specifically applied cathodal tDCS over the right dorsolateral prefrontal cortex. The majority of these studies employed variants of experimental procedures that assessed the ability to inhibit either inappropriate motor responses or competing memories during selective retrieval. In both domains, action stopping and memory downregulation, neuroimaging research has shown that successful inhibitory control engages common areas within the right lateral prefrontal cortex. Strikingly, although a significant proportion of the reviewed studies reported behavioral effects that can be interpreted as a consequence of hindering inhibitory control, they have not been previously considered or discussed altogether despite its theoretical and methodological implications. This consistent disruptive effect challenges the common belief that cathodal tDCS is ineffective in modulating performance when applied to prefrontal regions. Additionally, the results provide causal evidence that supports the proposed role of the right lateral prefrontal cortex in a domain-general inhibitory system, particularly in relation to stopping actions and downregulating competing memories.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"867 ","pages":"Article 138388"},"PeriodicalIF":2.0,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynamic current-clamp unveiling the indispensable interplay between Nav1.7 and Nav1.8 for shaping action potential trajectory and retaining neuroexcitation of visceral sensory neurons 动态电流钳揭示了Nav1.7和Nav1.8在形成动作电位轨迹和保持内脏感觉神经元神经兴奋方面不可或缺的相互作用。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-09-20 DOI: 10.1016/j.neulet.2025.138387

Ying Li , Chen Zhang , Limin Han , Zhao Qian

Tetrodotoxin (TTX)-sensitive/Nav1.7- and TTX-resistive/Nav1.8 Na⁺ channels contribute to neuroexcitation in the sensory neurons of the nodose ganglion (NG); however, their specific roles remain debatable. Therefore, we aimed to study the action potential (AP) elicited from NG neurons isolated from adult rats and simulated by a dynamic current clamp (DCC) using gNa0/Nav1.7 and/or gNa1/Nav1.8 injection. We trained and tuned the voltage-dependent profiles of the Na⁺ current generated from the DCC using the Hodgkin–Huxley/Vandenberg models to match the AP parameters elicited by a brief pulse. A- or C-type AP could be simulated using DCC by applying gNa0 or gNa0/gNa1 alongside reduced gNa0 to avoid overshooting the up-stroke. This indicates the indispensability of these two Na⁺ channels for shaping the AP trajectory with tight orchestration. The hump over the repolarization period featuring C-type neurons could be generated using DCC by adding gNa1 in this cellular model. Furthermore, both A- and C-type repeated discharges can be simulated using gNa0 or gNa1 with a reduced gNa0. Similar experiments were performed on human embryonic kidney 293 cells with stable Nav1.7 expression to mimic A-type-like conditions for further verification. Both A- and C-type-like APs were simulated in this expression system by adding gNa0 or gNa0/gNa1. Therefore, Nav1.7/Nav1.8 is crucial in shaping the AP trajectory, with specific timing for Nav1.8 activation to retain neuroexcitation in the sensory nervous system. Additionally, this pilot study will establish a fundamental base for the pharmacological screening of targeted ion channels and validate the disease-based mechanism in cardiology and neuroscience.

河豚毒素（TTX）敏感/Nav1.7-和TTX抵抗/Nav1.8 Na+通道参与结节神经节（NG）感觉神经元的神经兴奋；然而，它们的具体作用仍有争议。因此，我们旨在研究从成年大鼠分离的NG神经元引发的动作电位（AP），并使用gNa0/Nav1.7和/或gNa1/Nav1.8注射动态电流钳（DCC）模拟。我们使用霍奇金-赫胥黎/范登堡模型训练和调整了DCC产生的Na+电流的电压依赖谱，以匹配短脉冲引发的AP参数。A型或c型AP可以使用DCC模拟，通过施加gNa0或gNa0/gNa1以及减小的gNa0来避免上冲程过冲。这表明这两个Na+通道对于形成紧密编排的AP轨迹是不可或缺的。在细胞模型中加入gNa1后，DCC可以产生c型神经元复极期的驼峰。此外，A型和c型重复放电都可以用减小的gNa0或gNa1来模拟。在稳定表达Nav1.7的人胚胎肾293细胞上进行类似实验，模拟a型样条件，进一步验证。通过添加gNa0或gNa0/gNa1来模拟A型和c型ap。因此，Nav1.7/Nav1.8对于形成AP轨迹至关重要，通过特定的Nav1.8激活时间来保持感觉神经系统的神经兴奋。此外，本初步研究将为靶向离子通道的药理学筛选奠定基础，并在心脏病学和神经科学中验证基于疾病的机制。

{"title":"Dynamic current-clamp unveiling the indispensable interplay between Nav1.7 and Nav1.8 for shaping action potential trajectory and retaining neuroexcitation of visceral sensory neurons","authors":"Ying Li , Chen Zhang , Limin Han , Zhao Qian","doi":"10.1016/j.neulet.2025.138387","DOIUrl":"10.1016/j.neulet.2025.138387","url":null,"abstract":"<div><div>Tetrodotoxin (TTX)-sensitive/Nav1.7- and TTX-resistive/Nav1.8 Na<sup>+</sup> channels contribute to neuroexcitation in the sensory neurons of the nodose ganglion (NG); however, their specific roles remain debatable. Therefore, we aimed to study the action potential (AP) elicited from NG neurons isolated from adult rats and simulated by a dynamic current clamp (DCC) using gNa0/Nav1.7 and/or gNa1/Nav1.8 injection. We trained and tuned the voltage-dependent profiles of the Na<sup>+</sup> current generated from the DCC using the Hodgkin–Huxley/Vandenberg models to match the AP parameters elicited by a brief pulse. A- or C-type AP could be simulated using DCC by applying gNa0 or gNa0/gNa1 alongside reduced gNa0 to avoid overshooting the up-stroke. This indicates the indispensability of these two Na<sup>+</sup> channels for shaping the AP trajectory with tight orchestration. The hump over the repolarization period featuring C-type neurons could be generated using DCC by adding gNa1 in this cellular model. Furthermore, both A- and C-type repeated discharges can be simulated using gNa0 or gNa1 with a reduced gNa0. Similar experiments were performed on human embryonic kidney 293 cells with stable Nav1.7 expression to mimic A-type-like conditions for further verification. Both A- and C-type-like APs were simulated in this expression system by adding gNa0 or gNa0/gNa1. Therefore, Nav1.7/Nav1.8 is crucial in shaping the AP trajectory, with specific timing for Nav1.8 activation to retain neuroexcitation in the sensory nervous system. Additionally, this pilot study will establish a fundamental base for the pharmacological screening of targeted ion channels and validate the disease-based mechanism in cardiology and neuroscience.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"867 ","pages":"Article 138387"},"PeriodicalIF":2.0,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

COPII component Sec13 is required for peripheral myelination and Schwann cell maintenance COPII成分Sec13是外周髓鞘形成和雪旺细胞维持所必需的。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-09-17 DOI: 10.1016/j.neulet.2025.138386

Debao Wu , Zhenghao Li , Xiaoyun Lu , Li Li , Wenxiu Dai , Xuemin Wang , Liang Zhang

Peripheral nerve myelination critically relies on the timely and efficient delivery of myelin proteins and membranes. Although Coat Protein Complex II (COPII) is a canonical vesicular trafficking machinery, the cell-type-specific functions of its components in Schwann cell remain uncharacterized. Here, we show that Sec13, an essential component of COPII, is abundantly expressed in Schwann cells of the sciatic nerve. Furthermore, conditional knockout of Sec13 in Schwann cells (Sec13cKO) results in hindlimb weakness and lethality in mutant mice. Morphological analysis revealed that Sec13cKO nerves are thin and translucent, with immunostaining for myelin basic protein showing a progressive reduction in myelin coverage. Transmission electron microscopy demonstrated fewer myelinated axons, loosely wrapped or absent lamellae, and an increased g–ratio, indicating thinner, poorly compacted sheaths. At the cellular level, Sec13 deletion caused a marked decrease in Sox10⁺ Schwann cell density from P7 onward, concomitant with reduced proliferation of Sox10⁺, Sox2⁺, and Oct6⁺ populations, and a significant increase of cell death at P14. Together, these findings suggest that Sec13 is indispensable for Schwann cell proliferation, survival, and execution of the myelination program.

周围神经的髓鞘形成主要依赖于髓鞘蛋白和膜的及时有效的传递。虽然外壳蛋白复合物II （COPII）是一种典型的囊泡运输机制，但其组分在雪旺细胞中的细胞类型特异性功能仍未被表征。在这里，我们发现Sec13是COPII的一个重要组成部分，在坐骨神经的雪旺细胞中大量表达。此外，条件敲除雪旺细胞中的Sec13 （Sec13cKO）会导致突变小鼠后肢无力和死亡。形态学分析显示Sec13cKO神经薄而半透明，髓鞘碱性蛋白免疫染色显示髓鞘覆盖范围逐渐减少。透射电子显微镜显示髓鞘轴突较少，松散包裹或无片层，g比增加，表明鞘更薄，致密性差。在细胞水平上，从P7开始，Sec13缺失导致Sox10+雪旺细胞密度显著下降，同时Sox10+、Sox2+和Oct6+群体的增殖减少，P14时细胞死亡显著增加。总之，这些发现表明Sec13对于雪旺细胞的增殖、存活和髓鞘形成程序的执行是不可或缺的。

{"title":"COPII component Sec13 is required for peripheral myelination and Schwann cell maintenance","authors":"Debao Wu , Zhenghao Li , Xiaoyun Lu , Li Li , Wenxiu Dai , Xuemin Wang , Liang Zhang","doi":"10.1016/j.neulet.2025.138386","DOIUrl":"10.1016/j.neulet.2025.138386","url":null,"abstract":"<div><div>Peripheral nerve myelination critically relies on the timely and efficient delivery of myelin proteins and membranes. Although Coat Protein Complex II (COPII) is a canonical vesicular trafficking machinery, the cell-type-specific functions of its components in Schwann cell remain uncharacterized. Here, we show that Sec13, an essential component of COPII, is abundantly expressed in Schwann cells of the sciatic nerve. Furthermore, conditional knockout of Sec13 in Schwann cells (<em>Sec13</em>cKO) results in hindlimb weakness and lethality in mutant mice. Morphological analysis revealed that <em>Sec13</em>cKO nerves are thin and translucent, with immunostaining for myelin basic protein showing a progressive reduction in myelin coverage. Transmission electron microscopy demonstrated fewer myelinated axons, loosely wrapped or absent lamellae, and an increased <em>g</em>–ratio, indicating thinner, poorly compacted sheaths. At the cellular level, <em>Sec13</em> deletion caused a marked decrease in Sox10<sup>+</sup> Schwann cell density from P7 onward, concomitant with reduced proliferation of Sox10<sup>+</sup>, Sox2<sup>+</sup>, and Oct6<sup>+</sup> populations, and a significant increase of cell death at P14. Together, these findings suggest that Sec13 is indispensable for Schwann cell proliferation, survival, and execution of the myelination program.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"867 ","pages":"Article 138386"},"PeriodicalIF":2.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Acute restraint stress and epinephrine administration disrupt cognitive and emotional functions in male rats via modulation of proinflammatory cytokines, MCT-2, and neurogranin 急性约束应激和肾上腺素通过调节促炎细胞因子、MCT-2和神经颗粒蛋白破坏雄性大鼠的认知和情绪功能。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-09-08 DOI: 10.1016/j.neulet.2025.138382

Zehra Sezgin , Hale Sayan Ozacmak , Inci Turan

Stress triggers neuroendocrine and physiological changes, often resulting in cognitive impairments and heightened anxiety. This study aims to investigate the effects of acute stress and epinephrine administration on learning, memory, and anxiety-like behavior, as well as their impact on proinflammatory cytokines, neurogranin expression, and brain energy metabolism.

In this study, three experimental groups were established, each comprising eight rats: control, acute stress, and acute stress combined with epinephrine. The acute stress model consisted of 60 min of restraint stress. Epinephrine was administered following the stress procedure. Memory performance was evaluated using the Morris water maze (MWM), while anxiety-like behavior was assessed through the open field test (OFT). Levels of proinflammatory cytokines, neurogranin, MCT2, glycogen, and corticosterone levels were measured.

In the probe test, the acute stress group exhibited significantly poorer performance compared to the control group. Epinephrine administration induced anxiogenic effects in stressed animals. Neurogranin and glycogen levels in the hippocampus and prefrontal cortex were significantly reduced in rats exposed to stress + epinephrine compared to controls. MCT2 expression was also significantly lower in the stress + epinephrine group. IL-1β level was elevated in the prefrontal cortex of the stress + epinephrine group compared to the control group, while, TNF-α levels were found to be elevated in the hippocampus.

Epinephrine administration in conjunction with acute stress has been shown to reduce hippocampal levels of neurogranin, MCT-2, and glycogen, while simultaneously increasing proinflammatory cytokine levels. These molecular alterations appear to contribute to both impaired hippocampal-dependent learning and heightened anxiety-like behavior.

压力会引发神经内分泌和生理变化，通常会导致认知障碍和焦虑加剧。本研究旨在探讨急性应激和肾上腺素给药对学习、记忆和焦虑样行为的影响，以及它们对促炎细胞因子、神经颗粒蛋白表达和大脑能量代谢的影响。本研究建立3个实验组，每组8只大鼠：对照组、急性应激组、急性应激联合肾上腺素组。急性应力模型为60 min约束应力。在应激过程后给予肾上腺素。采用Morris水迷宫（MWM）评价记忆表现，采用open field test （OFT）评价类焦虑行为。测量促炎细胞因子、神经颗粒蛋白、MCT2、糖原和皮质酮水平。在探针测试中，急性应激组的表现明显低于对照组。肾上腺素给药诱导应激动物产生焦虑效应。与对照组相比，暴露于压力 + 肾上腺素的大鼠海马和前额皮质的神经颗粒蛋白和糖原水平显著降低。应激 + 肾上腺素组MCT2表达也显著降低。与对照组相比，应激 + 肾上腺素组前额叶皮层IL-1β水平升高，而海马中TNF-α水平升高。肾上腺素与急性应激联合使用已被证明可以降低海马神经颗粒蛋白、MCT-2和糖原的水平，同时增加促炎细胞因子的水平。这些分子改变似乎导致了海马依赖性学习受损和焦虑样行为加剧。

{"title":"Acute restraint stress and epinephrine administration disrupt cognitive and emotional functions in male rats via modulation of proinflammatory cytokines, MCT-2, and neurogranin","authors":"Zehra Sezgin , Hale Sayan Ozacmak , Inci Turan","doi":"10.1016/j.neulet.2025.138382","DOIUrl":"10.1016/j.neulet.2025.138382","url":null,"abstract":"<div><div>Stress triggers neuroendocrine and physiological changes, often resulting in cognitive impairments and heightened anxiety. This study aims to investigate the effects of acute stress and epinephrine administration on learning, memory, and anxiety-like behavior, as well as their impact on proinflammatory cytokines, neurogranin expression, and brain energy metabolism.</div><div>In this study, three experimental groups were established, each comprising eight rats: control, acute stress, and acute stress combined with epinephrine. The acute stress model consisted of 60 min of restraint stress. Epinephrine was administered following the stress procedure. Memory performance was evaluated using the Morris water maze (MWM), while anxiety-like behavior was assessed through the open field test (OFT). Levels of proinflammatory cytokines, neurogranin, MCT2, glycogen, and corticosterone levels were measured.</div><div>In the probe test, the acute stress group exhibited significantly poorer performance compared to the control group. Epinephrine administration induced anxiogenic effects in stressed animals. Neurogranin and glycogen levels in the hippocampus and prefrontal cortex were significantly reduced in rats exposed to stress + epinephrine compared to controls. MCT2 expression was also significantly lower in the stress + epinephrine group. IL-1β level was elevated in the prefrontal cortex of the stress + epinephrine group compared to the control group, while, TNF-α levels were found to be elevated in the hippocampus.</div><div>Epinephrine administration in conjunction with acute stress has been shown to reduce hippocampal levels of neurogranin, MCT-2, and glycogen, while simultaneously increasing proinflammatory cytokine levels. These molecular alterations appear to contribute to both impaired hippocampal-dependent learning and heightened anxiety-like behavior.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"867 ","pages":"Article 138382"},"PeriodicalIF":2.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0