Neuroscience最新文献_第5页

Short and long-term blockades of adenosine 2A, 5-HT2A, and 5-HT7 receptors induce apoptosis, reduce proliferation, and show differential effects on miR-27b-3p expression in neuroblastoma cell lines 短期和长期阻断腺苷 2A、5-HT2A 和 5-HT7 受体可诱导神经母细胞瘤细胞株凋亡、减少增殖，并对 miR-27b-3p 的表达产生不同影响。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-11-14 DOI: 10.1016/j.neuroscience.2024.11.032

Kemal Erdem Basaran , Seyda Korkmaz , Güzide Satır-Basaran , Hasan Salkın

The first of our aims in this study was to investigate the effects of 5-HT2AR, 5-HT7R, and A2AR blockades on miR-27b-3p expression in the short and long-term in neuroblastoma cells. Our second aim was to reduce the expression of pERK and suppress proliferation by blocking the 5-HT2AR with ketanserin. Our third aim was to reduce the expression of pAKT and induce apoptosis by blocking the A2AR and 5-HT7R with MSX3 and SB269970. Thus, we aimed to investigate the therapeutic efficacy of ketanserin, MSX3 and SB269970, individually or in combination, on neuroblastoma cells.

We found that short and long-term blockades of A2A, 5-HT2A, and 5-HT7 receptors had different effects on miR-27b-3p expression. Blockade of A2AR and 5-HT7R with MSX3 and SB269970 decreased miR-27b-3p expression in the short term while increasing it in the long term. Ketanserin increased miR-27b-3p expression in both the short and long term. When 5-HT2AR was blocked with ketanserin, no significant difference was observed in pERK expression and proliferation in the short term. In contrast, a substantial decrease in pERK expression and proliferation was detected in the long term. Our findings show that the MSX3 + SB269970 dual combination and ketanserin + MSX3 + SB269970 triple combination are especially critical in suppressing pAKT expression in the long term. These findings showed that pAKT protein expression induced apoptosis due to decreased in neuroblastoma cells.

Our study provides the first evidence for the relationships between ketanserin/miR-27b-3p/pERK, MSX3/miR-27b-3p/pAKT, and SB269970/miR-27b-3p/pAKT in neuroblastoma cells. Ketanserin, MSX3, and SB269970 drug combinations may be promising therapeutic agents in neuroblastoma cells.

本研究的第一个目的是研究 5-HT2AR、5-HT7R 和 A2AR 阻断对神经母细胞瘤细胞中 miR-27b-3p 表达的短期和长期影响。我们的第二个目的是通过酮塞林阻断 5-HT2AR 减少 pERK 的表达并抑制增殖。我们的第三个目标是通过使用 MSX3 和 SB269970 阻断 A2AR 和 5-HT7R 来减少 pAKT 的表达并诱导细胞凋亡。因此，我们旨在研究酮塞林、MSX3 和 SB269970 单独或联合使用对神经母细胞瘤细胞的疗效。我们发现，短期和长期阻断 A2A、5-HT2A 和 5-HT7 受体对 miR-27b-3p 的表达有不同的影响。用 MSX3 和 SB269970 阻断 A2AR 和 5-HT7R 会在短期内减少 miR-27b-3p 的表达，而在长期内则会增加。酮塞林能在短期和长期内增加 miR-27b-3p 的表达。当用酮塞林阻断 5-HT2AR 时，短期内 pERK 的表达和增殖没有明显差异。与此相反，pERK 的表达和增殖在长期内大幅减少。我们的研究结果表明，MSX3 + SB269970 双联疗法和酮塞林 + MSX3 + SB269970 三联疗法在长期抑制 pAKT 表达方面尤为关键。这些研究结果表明，神经母细胞瘤细胞中 pAKT 蛋白表达减少会诱导细胞凋亡。我们的研究首次证明了神经母细胞瘤细胞中酮色林/miR-27b-3p/pERK、MSX3/miR-27b-3p/pAKT和SB269970/miR-27b-3p/pAKT之间的关系。酮塞林、MSX3和SB269970药物组合可能是治疗神经母细胞瘤细胞的有效药物。

{"title":"Short and long-term blockades of adenosine 2A, 5-HT2A, and 5-HT7 receptors induce apoptosis, reduce proliferation, and show differential effects on miR-27b-3p expression in neuroblastoma cell lines","authors":"Kemal Erdem Basaran , Seyda Korkmaz , Güzide Satır-Basaran , Hasan Salkın","doi":"10.1016/j.neuroscience.2024.11.032","DOIUrl":"10.1016/j.neuroscience.2024.11.032","url":null,"abstract":"<div><div>The first of our aims in this study was to investigate the effects of 5-HT2AR, 5-HT7R, and A2AR blockades on miR-27b-3p expression in the short and long-term in neuroblastoma cells. Our second aim was to reduce the expression of pERK and suppress proliferation by blocking the 5-HT2AR with ketanserin. Our third aim was to reduce the expression of pAKT and induce apoptosis by blocking the A2AR and 5-HT7R with MSX3 and SB269970. Thus, we aimed to investigate the therapeutic efficacy of ketanserin, MSX3 and SB269970, individually or in combination, on neuroblastoma cells.</div><div>We found that short and long-term blockades of A2A, 5-HT2A, and 5-HT7 receptors had different effects on miR-27b-3p expression. Blockade of A2AR and 5-HT7R with MSX3 and SB269970 decreased miR-27b-3p expression in the short term while increasing it in the long term. Ketanserin increased miR-27b-3p expression in both the short and long term. When 5-HT2AR was blocked with ketanserin, no significant difference was observed in pERK expression and proliferation in the short term. In contrast, a substantial decrease in pERK expression and proliferation was detected in the long term. Our findings show that the MSX3 + SB269970 dual combination and ketanserin + MSX3 + SB269970 triple combination are especially critical in suppressing pAKT expression in the long term. These findings showed that pAKT protein expression induced apoptosis due to decreased in neuroblastoma cells.</div><div>Our study provides the first evidence for the relationships between ketanserin/miR-27b-3p/pERK, MSX3/miR-27b-3p/pAKT, and SB269970/miR-27b-3p/pAKT in neuroblastoma cells. Ketanserin, MSX3, and SB269970 drug combinations may be promising therapeutic agents in neuroblastoma cells.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"563 ","pages":"Pages 212-221"},"PeriodicalIF":2.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Eye movement disorders: A new approach to preliminary screening of Parkinson’s disease 眼球运动障碍：帕金森病初步筛查的新方法。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-11-14 DOI: 10.1016/j.neuroscience.2024.11.023

Han Li , Chengqian Li , Wenqi Ma , Kunpeng Qin , Zihan Wang , Binghui Hou , Anmu Xie

To investigate the characteristics and diagnostic values of the eye movement disorders in patients with Parkinson’s disease (PD-EMDs), this cross-sectional study enrolled 127 Chinese patients with PD and 80 healthy controls, and divided them into training and validation sets based on enrollment time. Performance in the five oculomotor paradigms was assessed using an infrared pupil and a corneal reflection tracking device. The primary characteristics of PD-EMDs were elucidated as inaccurate fixation with high deviation (frequency and total quantity); inaccurate saccades with delayed reaction and low velocity; saccadic pursuit with high deviation, delayed reaction, and velocity; and decreased visual search ability. Subgroup comparison shows that PD-EMDs can be related with PD stages, motor subtypes, frozen gait, and drowsiness. Finally, we developed and externally validated a model for PD preliminary screening using multivariate stepwise logistic regression analysis, comprising four oculomotor parameters (fixation accuracy, pro-saccade velocity, anti-saccade accuracy, and visual search duration), cognition score and educational years. The model has good feasibility with satisfactory performance on the receiver operating characteristic, calibration, and decision curves, and broad clinical applicability with better discrimination for more advanced PD patients and non-tremor-dominant PD patients. A nomogram was created to make the model more user-friendly in the clinical setting. Overall, we have demonstrated the presence of PD-EMDs and their prospective value for PD preliminary screening.

为了研究帕金森病患者眼球运动障碍（PD-EMDs）的特征和诊断价值，本横断面研究招募了127名中国帕金森病患者和80名健康对照者，并根据入组时间将他们分为训练集和验证集。研究人员使用红外线瞳孔仪和角膜反射跟踪仪对五种眼球运动范式的表现进行了评估。结果表明，PD-EMD 的主要特征为：定点不准，偏差大（频率和总量）；眼球移动不准，反应迟钝，速度慢；眼球追逐偏差大，反应迟钝，速度慢；视觉搜索能力下降。亚组比较显示，PD-EMDs 可与 PD 分期、运动亚型、冻结步态和嗜睡相关。最后，我们利用多变量逐步逻辑回归分析，建立了一个用于帕金森病初步筛查的模型，该模型由四个眼球运动参数（定点准确性、前眨眼速度、后眨眼准确性和视觉搜索持续时间）、认知评分和受教育年限组成，并进行了外部验证。该模型具有良好的可行性，在接受者操作特征曲线、校准曲线和决策曲线上都有令人满意的表现，并具有广泛的临床适用性，对晚期帕金森病患者和非肢体运动主导型帕金森病患者有更好的区分度。我们还创建了一个提名图，使该模型在临床环境中更易于使用。总之，我们已经证明了帕金森病EMDs的存在及其对帕金森病初步筛查的前瞻性价值。

{"title":"Eye movement disorders: A new approach to preliminary screening of Parkinson’s disease","authors":"Han Li , Chengqian Li , Wenqi Ma , Kunpeng Qin , Zihan Wang , Binghui Hou , Anmu Xie","doi":"10.1016/j.neuroscience.2024.11.023","DOIUrl":"10.1016/j.neuroscience.2024.11.023","url":null,"abstract":"<div><div>To investigate the characteristics and diagnostic values of the eye movement disorders in patients with Parkinson’s disease (PD-EMDs), this cross-sectional study enrolled 127 Chinese patients with PD and 80 healthy controls, and divided them into training and validation sets based on enrollment time. Performance in the five oculomotor paradigms was assessed using an infrared pupil and a corneal reflection tracking device. The primary characteristics of PD-EMDs were elucidated as inaccurate fixation with high deviation (frequency and total quantity); inaccurate saccades with delayed reaction and low velocity; saccadic pursuit with high deviation, delayed reaction, and velocity; and decreased visual search ability. Subgroup comparison shows that PD-EMDs can be related with PD stages, motor subtypes, frozen gait, and drowsiness. Finally, we developed and externally validated a model for PD preliminary screening using multivariate stepwise logistic regression analysis, comprising four oculomotor parameters (fixation accuracy, pro-saccade velocity, anti-saccade accuracy, and visual search duration), cognition score and educational years. The model has good feasibility with satisfactory performance on the receiver operating characteristic, calibration, and decision curves, and broad clinical applicability with better discrimination for more advanced PD patients and non-tremor-dominant PD patients. A nomogram was created to make the model more user-friendly in the clinical setting. Overall, we have demonstrated the presence of PD-EMDs and their prospective value for PD preliminary screening.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"563 ","pages":"Pages 202-211"},"PeriodicalIF":2.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hypocretin modulation of behavioral coping strategies for social stress 下视蛋白对社会压力行为应对策略的调节。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-11-14 DOI: 10.1016/j.neuroscience.2024.11.031

Pei X. Luo, Brian C. Trainor

Best known for promoting wakefulness and arousal, the neuropeptide hypocretin (Hcrt) also plays an important role in mediating stress responses, including social stress. However, central and systemic manipulation of the Hcrt system has produced diverse behavioral outcomes in animal models. In this review, we first focus on studies where similar manipulations of the Hcrt system led to divergent coping behaviors. We hypothesize that Hcrt differentially facilitates active and passive coping behaviors in response to social stress by acting in different brain regions and on different cell types. We then focus on region and cell type-specific effects of Hcrt in the ventral pallidum, lateral habenula, ventral tegmental area, nucleus accumbens, amygdala, and bed nucleus of the stria terminalis. Overall, the evidence suggests that rather than enhancing or inhibiting behavioral responses to social stress, Hcrt may signal the heightened arousal associated with stressful contexts. The resulting behavioral effects depend on which circuits Hcrt release occurs in and which receptor types are activated. Further study is needed to determine how and why circuit specific activation of Hcrt neurons occurs.

众所周知，神经肽下视素（Hcrt）具有促进觉醒和唤醒的作用，但它在介导应激反应（包括社会应激反应）方面也发挥着重要作用。然而，对 Hcrt 系统的中枢和系统操纵在动物模型中产生了不同的行为结果。在这篇综述中，我们首先关注对 Hcrt 系统的类似操作导致不同应对行为的研究。我们假设，Hcrt 通过作用于不同的大脑区域和不同的细胞类型，以不同的方式促进主动和被动应对社会压力的行为。随后，我们重点研究了Hcrt在腹侧苍白球、外侧哈文脑、腹侧被盖区、伏隔核、杏仁核和纹状体末端床核等区域和细胞类型的特异性效应。总之，这些证据表明，Hcrt 不是增强或抑制对社会压力的行为反应，而是发出与压力环境相关的高度唤醒信号。由此产生的行为效应取决于 Hcrt 在哪些回路释放以及哪些受体类型被激活。要确定 Hcrt 神经元的特定回路激活是如何发生的以及为什么会发生，还需要进一步的研究。

{"title":"Hypocretin modulation of behavioral coping strategies for social stress","authors":"Pei X. Luo, Brian C. Trainor","doi":"10.1016/j.neuroscience.2024.11.031","DOIUrl":"10.1016/j.neuroscience.2024.11.031","url":null,"abstract":"<div><div>Best known for promoting wakefulness and arousal, the neuropeptide hypocretin (Hcrt) also plays an important role in mediating stress responses, including social stress. However, central and systemic manipulation of the Hcrt system has produced diverse behavioral outcomes in animal models. In this review, we first focus on studies where similar manipulations of the Hcrt system led to divergent coping behaviors. We hypothesize that Hcrt differentially facilitates active and passive coping behaviors in response to social stress by acting in different brain regions and on different cell types. We then focus on region and cell type-specific effects of Hcrt in the ventral pallidum, lateral habenula, ventral tegmental area, nucleus accumbens, amygdala, and bed nucleus of the stria terminalis. Overall, the evidence suggests that rather than enhancing or inhibiting behavioral responses to social stress, Hcrt may signal the heightened arousal associated with stressful contexts. The resulting behavioral effects depend on which circuits Hcrt release occurs in and which receptor types are activated. Further study is needed to determine how and why circuit specific activation of Hcrt neurons occurs.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"564 ","pages":"Pages 126-134"},"PeriodicalIF":2.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Semaglutide promotes the transition of microglia from M1 to M2 type to reduce brain inflammation in APP/PS1/tau mice 塞马鲁肽能促进小胶质细胞从M1型向M2型转变，从而减轻APP/PS1/tau小鼠的脑部炎症。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-11-14 DOI: 10.1016/j.neuroscience.2024.11.022

Zhao-Jun Wang , Wei-Na Han , Shi-Fan Chai , Yan Li , Chao-Jing Fu , Chen-Fang Wang , Hong-Yan Cai , Xin-Yi Li , Xiao Wang , Christian Hölscher , Mei-Na Wu

A growing number of studies show that the diabetes drug Semaglutide is neuroprotective in Alzheimer’s disease (AD) animal models, but its mode of action is not fully understood. In order to explore the mechanism of Semaglutide, 7-month-old APP/PS1/tau transgenic (3xTg) mice and wild-type (WT) mice were randomly divided into four groups: control group (WT + PBS), AD model group (3xTg + PBS), Semaglutide control group (WT + Semaglutide) and Semaglutide treatment group (3xTg + Semaglutide). Semaglutide (25 nmol/kg) or PBS was administered intraperitoneally once every two days for 30 days, followed by behavioral and molecular experiments. The results show that Semaglutide can improve working memory and spatial reference memory of 3xTg-AD mice, promote the release of anti-inflammatory factors and inhibit the production of pro-inflammatory factors in the cortex and hippocampus, and reduce Aβ deposition in the hippocampal CA1 region of 3xTg mice. Semaglutide can inhibit the apoptosis of BV2 cells induced by Aβ1-42 in a dose-dependent manner and promote the transformation of microglia from M1 to M2, thereby exerting anti-inflammatory and neuroprotective effects. Therefore, we speculate that Semaglutide shows an anti-inflammatory effect by promoting the transformation of microglia from M1 to M2 type in the brain of 3xTg mice, and thus exerts a neuroprotective effect.

越来越多的研究表明，糖尿病药物塞马鲁肽对阿尔茨海默病（AD）动物模型具有神经保护作用，但其作用模式尚未完全清楚。为了探索塞马鲁肽的作用机制，研究人员将7个月大的APP/PS1/tau转基因（3xTg）小鼠和野生型（WT）小鼠随机分为四组：对照组（WT + PBS）、AD模型组（3xTg + PBS）、塞马鲁肽对照组（WT + 塞马鲁肽）和塞马鲁肽治疗组（3xTg + 塞马鲁肽）。每两天腹腔注射一次塞马鲁肽（25 nmol/kg）或PBS，持续30天，然后进行行为和分子实验。结果表明，塞马鲁肽能改善3xTg-AD小鼠的工作记忆和空间参照记忆，促进皮层和海马中抗炎因子的释放并抑制促炎因子的产生，减少3xTg小鼠海马CA1区的Aβ沉积。塞马鲁肽能以剂量依赖的方式抑制Aβ1-42诱导的BV2细胞凋亡，并促进小胶质细胞从M1向M2转化，从而发挥抗炎和神经保护作用。因此，我们推测塞马鲁肽是通过促进3xTg小鼠脑内小胶质细胞从M1型向M2型转化而产生抗炎作用，从而发挥神经保护作用的。

{"title":"Semaglutide promotes the transition of microglia from M1 to M2 type to reduce brain inflammation in APP/PS1/tau mice","authors":"Zhao-Jun Wang , Wei-Na Han , Shi-Fan Chai , Yan Li , Chao-Jing Fu , Chen-Fang Wang , Hong-Yan Cai , Xin-Yi Li , Xiao Wang , Christian Hölscher , Mei-Na Wu","doi":"10.1016/j.neuroscience.2024.11.022","DOIUrl":"10.1016/j.neuroscience.2024.11.022","url":null,"abstract":"<div><div>A growing number of studies show that the diabetes drug Semaglutide is neuroprotective in Alzheimer’s disease (AD) animal models, but its mode of action is not fully understood. In order to explore the mechanism of Semaglutide, 7-month-old APP/PS1/tau transgenic (3xTg) mice and wild-type (WT) mice were randomly divided into four groups: control group (WT + PBS), AD model group (3xTg + PBS), Semaglutide control group (WT + Semaglutide) and Semaglutide treatment group (3xTg + Semaglutide). Semaglutide (25 nmol/kg) or PBS was administered intraperitoneally once every two days for 30 days, followed by behavioral and molecular experiments. The results show that Semaglutide can improve working memory and spatial reference memory of 3xTg-AD mice, promote the release of anti-inflammatory factors and inhibit the production of pro-inflammatory factors in the cortex and hippocampus, and reduce Aβ deposition in the hippocampal CA1 region of 3xTg mice. Semaglutide can inhibit the apoptosis of BV2 cells induced by Aβ1-42 in a dose-dependent manner and promote the transformation of microglia from M1 to M2, thereby exerting anti-inflammatory and neuroprotective effects. Therefore, we speculate that Semaglutide shows an anti-inflammatory effect by promoting the transformation of microglia from M1 to M2 type in the brain of 3xTg mice, and thus exerts a neuroprotective effect.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"563 ","pages":"Pages 222-234"},"PeriodicalIF":2.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Central treatment of neuropeptide-S attenuates cognitive dysfunction and hippocampal synaptic plasticity impairment by increasing CaMKII/GluR1 in hemiparkinsonian rats 通过增加CaMKII/GluR1，中枢治疗神经肽-S可减轻半帕金森大鼠的认知功能障碍和海马突触可塑性损伤。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-11-14 DOI: 10.1016/j.neuroscience.2024.11.021

Osman Sinen , Ayşegül Gemici Sinen , Narin Derin

Neuropeptide-S (NPS) has been demonstrated to mitigate learning and memory deficits in experimental models of Parkinson’s Disease (PD). Despite this, the precise mechanisms through which NPS exerts its influence on cognitive functions remain to be fully unknown. This study aims to elucidate the effects of central administration of NPS on learning and memory deficits associated with an experimental rat hemiparkinsonian model, examining both electrophysiological and molecular parameters. The hemiparkinsonian model was established via stereotactic injection of 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle. Central NPS (1 nmol, icv) was administered into the lateral ventricle via a cannula for seven consecutive days following the 6-OHDA lesion. The Morris water maze and object recognition tests were used to evaluate the rat’s learning and memory abilities. Long-term potentiation (LTP) recordings were conducted to assess hippocampal synaptic plasticity. Immunohistochemistry was employed to determine the expression levels of phosphorylated CaMKII (pCaMKII), GluR1, and GluR2 in the hippocampus. The 6-OHDA-induced decline in cognitive performance was significantly (p < 0.05) improved in rats that received central NPS. In 6-OHDA-lesioned rats, NPS treatment significantly (p < 0.05) enhanced the amplitude of LTP at the dentate gyrus/perforant path synapses. Furthermore, NPS significantly (p < 0.05) increased the number of pCaMKII and GluR1 immunoreactive cells in the hippocampus, which had been diminished due to 6-OHDA, except for GluR2 levels. These findings provide insight into the mechanisms by which central NPS administration enhances cognitive functions in an experimental model of PD, highlighting its potential therapeutic benefits for addressing cognitive deficits in PD.

神经肽-S（NPS）已被证明可以减轻帕金森病（PD）实验模型中的学习和记忆缺陷。尽管如此，NPS对认知功能产生影响的确切机制仍然完全未知。本研究旨在阐明中枢给药 NPS 对与实验性大鼠半帕金森病模型相关的学习和记忆障碍的影响，同时检查电生理学和分子参数。半帕金森病模型是通过向右侧内侧前脑束立体定向注射 6-羟基多巴胺（6-OHDA）建立的。在6-OHDA病变后连续七天通过插管向侧脑室注射中枢NPS（1 nmol，icv）。莫里斯水迷宫和物体识别测试用于评估大鼠的学习和记忆能力。长期电位（LTP）记录用于评估海马突触可塑性。免疫组化法测定了磷酸化 CaMKII（pCaMKII）、GluR1 和 GluR2 在海马中的表达水平。6-OHDA诱导的认知能力下降显著（p

{"title":"Central treatment of neuropeptide-S attenuates cognitive dysfunction and hippocampal synaptic plasticity impairment by increasing CaMKII/GluR1 in hemiparkinsonian rats","authors":"Osman Sinen , Ayşegül Gemici Sinen , Narin Derin","doi":"10.1016/j.neuroscience.2024.11.021","DOIUrl":"10.1016/j.neuroscience.2024.11.021","url":null,"abstract":"<div><div>Neuropeptide-S (NPS) has been demonstrated to mitigate learning and memory deficits in experimental models of Parkinson’s Disease (PD). Despite this, the precise mechanisms through which NPS exerts its influence on cognitive functions remain to be fully unknown. This study aims to elucidate the effects of central administration of NPS on learning and memory deficits associated with an experimental rat hemiparkinsonian model, examining both electrophysiological and molecular parameters. The hemiparkinsonian model was established via stereotactic injection of 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle. Central NPS (1 nmol, icv) was administered into the lateral ventricle via a cannula for seven consecutive days following the 6-OHDA lesion. The Morris water maze and object recognition tests were used to evaluate the rat’s learning and memory abilities. Long-term potentiation (LTP) recordings were conducted to assess hippocampal synaptic plasticity. Immunohistochemistry was employed to determine the expression levels of phosphorylated CaMKII (pCaMKII), GluR1, and GluR2 in the hippocampus. The 6-OHDA-induced decline in cognitive performance was significantly (p < 0.05) improved in rats that received central NPS. In 6-OHDA-lesioned rats, NPS treatment significantly (p < 0.05) enhanced the amplitude of LTP at the dentate gyrus/perforant path synapses. Furthermore, NPS significantly (p < 0.05) increased the number of pCaMKII and GluR1 immunoreactive cells in the hippocampus, which had been diminished due to 6-OHDA, except for GluR2 levels. These findings provide insight into the mechanisms by which central NPS administration enhances cognitive functions in an experimental model of PD, highlighting its potential therapeutic benefits for addressing cognitive deficits in PD.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"564 ","pages":"Pages 194-201"},"PeriodicalIF":2.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dietary interventions in mitigating the impact of environmental pollutants on Alzheimer’s disease – A review 减轻环境污染物对阿尔茨海默病影响的膳食干预--综述。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-11-13 DOI: 10.1016/j.neuroscience.2024.11.020

Pratima Khandayataray , Meesala Krishna Murthy

Numerous studies linking environmental pollutants to oxidative stress, inflammation, and neurotoxicity have assigned pollutants to several neurodegenerative disorders, including Alzheimer’s disease (AD). Heavy metals, pesticides, air pollutants, and endocrine disruptor chemicals have been shown to play important roles in AD development, with some traditional functions in amyloid-β formation, tau kinase action, and neuronal degeneration. However, pharmacological management and supplementation have resulted in limited improvement. This raises the interesting possibility that activities usually considered preventive, including diet, exercise, or mental activity, might be more similar to treatment or therapy for AD. This review focuses on the effects of diet on the effects of environmental pollutants on AD. One of the primary issues addressed in this review is a group of specific diets, including the Mediterranean diet (MeDi), Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH intervention for Neurodegenerative Delay (MIND), which prevent exposure to these toxins. Such diets have been proven to decrease oxidative stress and inflammation, which are unfavorable for neuronal growth. Furthermore, they contribute to positive changes in the composition of the human gut microbiota and thus encourage interactions in the Gut-Brain Axis, reducing inflammation caused by pollutants. This review emphasizes a multi-professional approach with reference to nutritional activities that would lower the neurotoxic load in populations with a high level of exposure to pollutants. Future studies focusing on diet and environment association plans may help identify preventive measures aimed at enhancing current disease deceleration.

大量研究将环境污染物与氧化应激、炎症和神经毒性联系起来，并将污染物与包括阿尔茨海默病（AD）在内的多种神经退行性疾病联系起来。重金属、杀虫剂、空气污染物和内分泌干扰化学物质已被证明在阿尔茨海默病的发展过程中扮演重要角色，其中一些传统功能包括淀粉样蛋白-β的形成、tau激酶作用和神经元变性。然而，药物治疗和补充剂只能带来有限的改善。这就提出了一个有趣的可能性，即通常被认为是预防性的活动，包括饮食、运动或脑力活动，可能更类似于对注意力缺失症的治疗或疗法。本综述侧重于饮食对环境污染物对注意力缺失症的影响。本综述涉及的主要问题之一是一组特定饮食，包括地中海饮食（MeDi）、膳食疗法（DASH）和地中海-DASH 神经退行性延迟干预（MIND），这些饮食可防止接触这些毒素。事实证明，这些饮食能减少氧化应激和炎症，而氧化应激和炎症不利于神经元的生长。此外，它们还有助于人类肠道微生物群组成的积极变化，从而促进肠道-大脑轴的相互作用，减少污染物引起的炎症。这篇综述强调了一种多专业的方法，即参考营养活动，降低高浓度暴露于污染物的人群的神经毒性负荷。未来以饮食与环境关联计划为重点的研究可能有助于确定预防措施，以加强当前的疾病减速工作。

{"title":"Dietary interventions in mitigating the impact of environmental pollutants on Alzheimer’s disease – A review","authors":"Pratima Khandayataray , Meesala Krishna Murthy","doi":"10.1016/j.neuroscience.2024.11.020","DOIUrl":"10.1016/j.neuroscience.2024.11.020","url":null,"abstract":"<div><div>Numerous studies linking environmental pollutants to oxidative stress, inflammation, and neurotoxicity have assigned pollutants to several neurodegenerative disorders, including Alzheimer’s disease (AD). Heavy metals, pesticides, air pollutants, and endocrine disruptor chemicals have been shown to play important roles in AD development, with some traditional functions in amyloid-β formation, tau kinase action, and neuronal degeneration. However, pharmacological management and supplementation have resulted in limited improvement. This raises the interesting possibility that activities usually considered preventive, including diet, exercise, or mental activity, might be more similar to treatment or therapy for AD. This review focuses on the effects of diet on the effects of environmental pollutants on AD. One of the primary issues addressed in this review is a group of specific diets, including the Mediterranean diet (MeDi), Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH intervention for Neurodegenerative Delay (MIND), which prevent exposure to these toxins. Such diets have been proven to decrease oxidative stress and inflammation, which are unfavorable for neuronal growth. Furthermore, they contribute to positive changes in the composition of the human gut microbiota and thus encourage interactions in the Gut-Brain Axis, reducing inflammation caused by pollutants. This review emphasizes a multi-professional approach with reference to nutritional activities that would lower the neurotoxic load in populations with a high level of exposure to pollutants. Future studies focusing on diet and environment association plans may help identify preventive measures aimed at enhancing current disease deceleration.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"563 ","pages":"Pages 148-166"},"PeriodicalIF":2.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Relationship between initial motor variability and learning and adaptive ability. A systematic review. 初始运动变异性与学习和适应能力之间的关系。系统综述。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-11-13 DOI: 10.1016/j.neuroscience.2024.10.052

Miguel López-Fernández, Rafael Sabido, Carla Caballero, Francisco J Moreno

Motor variability is an intrinsic feature of human beings that has been associated with the ability for learning and adaptation to specific tasks. The purpose of this review is to examine whether there is a possible direct relationship between individuals' initial variability, in both amount and structure variability, in their ability for learning and adaptation in motor tasks. Eighteen articles examined the relationship between initial motor variability and the ability for learning and adaptation. Twelve found a direct relationship. In reward learning task greater amount variability was associated with greater improvement learning, however, this association was not observed with structure variability. While in error learning task associations were reported with both greater amount variability and more complexity structure. Nevertheless, bias in initial performance related to the amount of variability was found, so the structure of initial variability seems to be a better indicator of improvement in this type of task. Further research is needed for further research to better understand the potential relationship between initial motor variability and the ability for learning and adaptation in motor tasks.

运动变异性是人类的固有特征，与特定任务的学习和适应能力有关。本综述旨在研究个体的初始变异性（包括数量和结构变异性）与其在运动任务中的学习和适应能力之间是否可能存在直接关系。有 18 篇文章研究了初始运动变异性与学习和适应能力之间的关系。其中 12 篇发现两者之间存在直接关系。在奖励学习任务中，数量变异性越大，学习进步越大，但结构变异性却没有发现这种关联。而在错误学习任务中，据报告数量变异性越大，结构越复杂，两者都有关联。然而，我们发现初始成绩的偏差与变异量有关，因此初始变异的结构似乎是这类任务中提高成绩的更好指标。要想更好地了解初始运动变异性与运动任务中的学习和适应能力之间的潜在关系，还需要进一步的研究。

{"title":"Relationship between initial motor variability and learning and adaptive ability. A systematic review.","authors":"Miguel López-Fernández, Rafael Sabido, Carla Caballero, Francisco J Moreno","doi":"10.1016/j.neuroscience.2024.10.052","DOIUrl":"https://doi.org/10.1016/j.neuroscience.2024.10.052","url":null,"abstract":"<p><p>Motor variability is an intrinsic feature of human beings that has been associated with the ability for learning and adaptation to specific tasks. The purpose of this review is to examine whether there is a possible direct relationship between individuals' initial variability, in both amount and structure variability, in their ability for learning and adaptation in motor tasks. Eighteen articles examined the relationship between initial motor variability and the ability for learning and adaptation. Twelve found a direct relationship. In reward learning task greater amount variability was associated with greater improvement learning, however, this association was not observed with structure variability. While in error learning task associations were reported with both greater amount variability and more complexity structure. Nevertheless, bias in initial performance related to the amount of variability was found, so the structure of initial variability seems to be a better indicator of improvement in this type of task. Further research is needed for further research to better understand the potential relationship between initial motor variability and the ability for learning and adaptation in motor tasks.</p>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dopamine-D2-agonist targets mitochondrial dysfunction via diminishing Drp1 mediated fission and normalizing PGC1-α/SIRT3 pathways in a rodent model of Subarachnoid Haemorrhage 在蛛网膜下腔出血的啮齿动物模型中，多巴胺-D2-受体激动剂通过减少 Drp1 介导的裂变和使 PGC1-α/SIRT3 通路正常化来靶向线粒体功能障碍。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-11-13 DOI: 10.1016/j.neuroscience.2024.11.028

Ahmed Shaney Rehman , Pravir Kumar , Suhel Parvez

The adverse impact of disturb mitochondrial biogenesis on early brain injury (EBI) following subarachnoid haemorrhage (SAH) has been broadly recognized and is closely associated with oxidative stress and neuronal apoptosis. Previous studies have indicated the therapeutic potential of Ropinirole, a dopamine D2 agonist, in Ischemic Stroke. However, there is a lack of evidence regarding the ability of Ropinirole to enhance mitochondrial biogenesis and quality control after subarachnoid haemorrhage. The objective of this study is to investigate the effects of Ropinirole specific doses (10 & 20 mg/kg b. wt.) on mitochondria dysfunction in endovascular perforation SAH model in male Wistar rat. An endovascular perforation model was established using male Wistar rats that had sustained SAH injury. After the SAH injury, SAH grading on blood clot, Nissl staining, and neurobehavioral assessment were used to determine the severity. ROS and MMP, which are indicators of oxidative stress, were examined using flow cytometry. The findings demonstrated that the use of Ropinirole improved neurobehavioral outcomes, decreased brain edema, and reduced oxidative stress and mitochondrial based apoptosis. Further research showed that, Ropinirole therapy inhibit Drp1-mediated fission by accelerating the activity of fusion protein Mfn2/OPA1 along with regulating the translocation of PGC1-α and SIRT3 through restricting cytochrome C inside mitochondria to maintain mitochondrial metabolism. Ropinirole exerted neuroprotective effects by improving mitochondrial activity in a PGC1-α/SIRT3-dependent way via regulating Drp1 mediated fission. The effective treatment for SAH-induced EBI may involve increasing biogenesis and inhibiting excessive mitochondrial fission with Ropinirole.

蛛网膜下腔出血（SAH）后早期脑损伤（EBI）的不良影响已得到广泛认可，这与氧化应激和神经元凋亡密切相关。以往的研究表明，罗匹尼罗对缺血性中风具有治疗潜力。然而，关于罗匹尼罗在蛛网膜下腔出血后增强线粒体生物生成和质量控制的能力还缺乏证据。本研究旨在探讨特定剂量（10 和 20 毫克/千克体重）的罗匹尼罗对雄性 Wistar 大鼠血管内穿孔 SAH 模型线粒体功能障碍的影响。利用雄性 Wistar 大鼠的 SAH 损伤建立了血管内穿孔模型。SAH损伤后，通过血凝块分级、Nissl染色和神经行为评估来确定SAH的严重程度。使用流式细胞术检测了氧化应激指标 ROS 和 MMP。研究结果表明，使用罗匹尼罗能改善神经行为结果，减轻脑水肿，减少氧化应激和线粒体凋亡。进一步的研究表明，罗匹尼罗疗法通过加速融合蛋白 Mfn2/OPA1 的活性来抑制 Drp1 介导的裂变，同时通过限制线粒体内的细胞色素 C 来调节 PGC1-α 和 SIRT3 的转位，从而维持线粒体的新陈代谢。罗匹尼罗通过调节 Drp1 介导的裂变，以 PGC1-α/SIRT3 依赖性方式改善线粒体活性，从而发挥神经保护作用。治疗 SAH 引起的 EBI 的有效方法可能包括用罗匹尼罗增加生物生成和抑制线粒体的过度裂变。

{"title":"Dopamine-D2-agonist targets mitochondrial dysfunction via diminishing Drp1 mediated fission and normalizing PGC1-α/SIRT3 pathways in a rodent model of Subarachnoid Haemorrhage","authors":"Ahmed Shaney Rehman , Pravir Kumar , Suhel Parvez","doi":"10.1016/j.neuroscience.2024.11.028","DOIUrl":"10.1016/j.neuroscience.2024.11.028","url":null,"abstract":"<div><div>The adverse impact of disturbmitochondrialbiogenesis onearly brain injury (EBI) following subarachnoid haemorrhage (SAH) has been broadly recognized and is closely associated with oxidative stress and neuronal apoptosis. Previous studies have indicated the therapeutic potential of Ropinirole, a dopamine D2 agonist, in Ischemic Stroke. However, there is a lack of evidence regarding the ability of Ropinirole to enhance mitochondrial biogenesis and quality control after subarachnoid haemorrhage. The objective of this study is to investigate the effects of Ropinirole specific doses (10 & 20 mg/kg b. wt.) on mitochondria dysfunction in endovascular perforation SAH model in male Wistar rat. An endovascular perforation model was established using male Wistar rats that had sustained SAH injury. After the SAH injury, SAH grading on blood clot, Nissl staining, and neurobehavioral assessment were used to determine the severity. ROS and MMP, which are indicators of oxidative stress, were examined using flow cytometry. The findings demonstrated that the use of Ropinirole improved neurobehavioral outcomes, decreased brain edema, and reduced oxidative stress and mitochondrial based apoptosis. Further research showed that, Ropinirole therapy inhibit Drp1-mediated fission by accelerating the activity of fusion protein Mfn2/OPA1 along with regulating the translocation of PGC1-α and SIRT3 through restricting cytochrome <em>C</em> inside mitochondria to maintain mitochondrial metabolism. Ropinirole exerted neuroprotective effects by improving mitochondrial activity in a PGC1-α/SIRT3-dependent way via regulating Drp1 mediated fission. The effective treatment for SAH-induced EBI may involve increasing biogenesis and inhibiting excessive mitochondrial fission with Ropinirole.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"564 ","pages":"Pages 60-78"},"PeriodicalIF":2.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pretreatment with tetramethylpyrazine alleviated the impairment of learning and memory induced by sevoflurane exposure in neonatal rats. 四甲基吡嗪的预处理减轻了七氟醚暴露对新生大鼠学习和记忆的损害。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-11-12 DOI: 10.1016/j.neuroscience.2024.11.013

Kui Wang, Haidong Wei, Liufei Yang, Shuyue Zhang, Yiqin Cheng, Chen Li, Pengyu Jia, Yuanyuan Zhang, Yan Zhang, Pei Fan, Ning Wang, Haixia Lu, Xinlin Chen, Yong Liu, Pengbo Zhang

Sevoflurane impairs learning and memory of the developing brain. However, strategies to mitigate these detrimental effects have been scarce. Herein, we investigated whether tetramethylpyrazine could alleviate the impairment of learning and memory and its underlying mechanisim in sevoflurane-exposed neonatal rats. Postnatal 7-day Sprague-Dawley (SD) rats or primary hippocampal neurons were pretreated with tetramethylpyrazine and then exposed to sevoflurane. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and lactate dehydrogenase (LDH) assays were used to detect neuronal injury. Learning and memory function were evaluated by novel object recognition and Morris water maze tests. Long-term potentiation (LTP) was recorded to evaluate synaptic plasticity electrophysiologically in the hippocampal slices. Golgi-Cox staining or PSD95 immunochemistry was used to detect the morphology of dendritic spines. Western blotting was employed to assess the expressions of cleaved Caspase-3, PSD95, NMDAR1, NMDAR2A and NMDAR2B in the hippocampus or cultured neurons. It was found that neonatal exposure of sevoflurane impaired learning and memory, increased neuronal apoptosis, altered the morphology of dendritic spine, upregulated the expressions of NMDAR2A and PSD95, and induced LTP deficits. Pretreatment with tetramethylpyrazine not only alleviated impairment of learning and memory, but also improved sevoflurane-induced changes in neuronal damage, dendritic spine morphology, NMDAR2A and PSD95 expressions, as well as LTP. These findings indicated that pretreatment with tetramethylpyrazine alleviated the impairment of learning and memory induced by sevoflurane through improvement of hippocampal synaptic plasticity in neonatal rats.

七氟烷会损害发育中大脑的学习和记忆。然而，减轻这些有害影响的策略却很少见。在此，我们研究了四甲基吡嗪是否能减轻七氟醚暴露的新生大鼠的学习和记忆损伤及其潜在机制。用四甲基吡嗪预处理出生后7天的Sprague-Dawley（SD）大鼠或初级海马神经元，然后将其暴露于七氟烷中。末端脱氧核苷酸转移酶介导的 dUTP 缺口标记（TUNEL）和乳酸脱氢酶（LDH）检测法用于检测神经元损伤。学习和记忆功能通过新物体识别和莫里斯水迷宫测试进行评估。通过记录海马切片的长期电位（LTP）来评估突触的电生理学可塑性。高尔基-考克斯染色法或 PSD95 免疫化学法用于检测树突棘的形态。用 Western 印迹法评估海马或培养神经元中 Caspase-3、PSD95、NMDAR1、NMDAR2A 和 NMDAR2B 的表达。研究发现，新生儿暴露于七氟烷会损害学习和记忆，增加神经元凋亡，改变树突棘的形态，上调 NMDAR2A 和 PSD95 的表达，并诱导 LTP 缺陷。四甲基吡嗪预处理不仅能缓解学习和记忆障碍，还能改善七氟醚诱导的神经元损伤、树突棘形态、NMDAR2A和PSD95表达以及LTP变化。这些研究结果表明，四甲基吡嗪可通过改善新生大鼠海马突触的可塑性来缓解七氟醚引起的学习和记忆损伤。

{"title":"Pretreatment with tetramethylpyrazine alleviated the impairment of learning and memory induced by sevoflurane exposure in neonatal rats.","authors":"Kui Wang, Haidong Wei, Liufei Yang, Shuyue Zhang, Yiqin Cheng, Chen Li, Pengyu Jia, Yuanyuan Zhang, Yan Zhang, Pei Fan, Ning Wang, Haixia Lu, Xinlin Chen, Yong Liu, Pengbo Zhang","doi":"10.1016/j.neuroscience.2024.11.013","DOIUrl":"https://doi.org/10.1016/j.neuroscience.2024.11.013","url":null,"abstract":"<p><p>Sevoflurane impairs learning and memory of the developing brain. However, strategies to mitigate these detrimental effects have been scarce. Herein, we investigated whether tetramethylpyrazine could alleviate the impairment of learning and memory and its underlying mechanisim in sevoflurane-exposed neonatal rats. Postnatal 7-day Sprague-Dawley (SD) rats or primary hippocampal neurons were pretreated with tetramethylpyrazine and then exposed to sevoflurane. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and lactate dehydrogenase (LDH) assays were used to detect neuronal injury. Learning and memory function were evaluated by novel object recognition and Morris water maze tests. Long-term potentiation (LTP) was recorded to evaluate synaptic plasticity electrophysiologically in the hippocampal slices. Golgi-Cox staining or PSD95 immunochemistry was used to detect the morphology of dendritic spines. Western blotting was employed to assess the expressions of cleaved Caspase-3, PSD95, NMDAR1, NMDAR2A and NMDAR2B in the hippocampus or cultured neurons. It was found that neonatal exposure of sevoflurane impaired learning and memory, increased neuronal apoptosis, altered the morphology of dendritic spine, upregulated the expressions of NMDAR2A and PSD95, and induced LTP deficits. Pretreatment with tetramethylpyrazine not only alleviated impairment of learning and memory, but also improved sevoflurane-induced changes in neuronal damage, dendritic spine morphology, NMDAR2A and PSD95 expressions, as well as LTP. These findings indicated that pretreatment with tetramethylpyrazine alleviated the impairment of learning and memory induced by sevoflurane through improvement of hippocampal synaptic plasticity in neonatal rats.</p>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plasma fibroblast growth factor 21 and risk of cognitive impairment among patients with ischemic stroke 血浆成纤维细胞生长因子 21 与缺血性中风患者认知障碍的风险。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-11-12 DOI: 10.1016/j.neuroscience.2024.11.012

Xiaowei Zheng , Zhengbao Zhu , Chongke Zhong , Daoxia Guo , Xiaoqing Bu , Hao Peng , Tan Xu , Yonghong Zhang

Background and aims

Previous study reported that plasma fibroblast growth factor 21 (FGF-21) was associated with poor prognosis in patients with ischemic stroke. The purpose of present study was to prospectively investigate the relationship between plasma FGF-21 and post-stroke cognitive impairment (PSCI).

Methods

A total of 600 patients from 7 hospitals were included in this study and plasma FGF-21 levels were examined for all the participants. Cognitive impairment was evaluated using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at 3 months after ischemic stroke onset.

Results

323(53.8 %) or 419(69.8 %) participants had PSCI according to MMSE or MoCA at 3 months, respectively. After adjustment for age, National Institutes of Health stroke score, education, and other covariates, the odds ratio of PSCI defined by MMSE and MoCA for the highest vs lowest quartile of plasma FGF-21 was 1.77(1.05–2.98) and 2.40(1.35–4.29), respectively. Multiple-adjusted spline regression model showed a linear association between FGF-21 levels and PSCI (all P < 0.005 for linearity). Subgroup analyses further confirmed these results.

Conclusion

Elevated plasma FGF-21 level was associated with PSCI at 3 months after stroke independently of established conventional risk factors, suggesting that plasma FGF-21 may have potential prognostic value in risk stratification of PSCI.

背景与目的：先前的研究报道血浆成纤维细胞生长因子21（FGF-21）与缺血性卒中患者的不良预后有关。本研究旨在前瞻性地探讨血浆成纤维细胞生长因子 21 与脑卒中后认知障碍（PSCI）之间的关系：本研究共纳入了来自 7 家医院的 600 名患者，并对所有参与者的血浆 FGF-21 水平进行了检测。缺血性脑卒中发病 3 个月后，使用迷你精神状态检查（MMSE）和蒙特利尔认知评估（MoCA）对认知障碍进行评估：根据 3 个月时的 MMSE 或 MoCA，分别有 323 人（53.8%）或 419 人（69.8%）患有 PSCI。在对年龄、美国国立卫生研究院卒中评分、教育程度和其他协变量进行调整后，血浆 FGF-21 的最高四分位数与最低四分位数在 MMSE 和 MoCA 中定义的 PSCI 的几率比分别为 1.77（1.05-2.98）和 2.40（1.35-4.29）。多重调整曲线回归模型显示，FGF-21水平与PSCI之间存在线性关系（均为P 结论：血浆FGF-21水平升高与PSCI之间存在线性关系：血浆 FGF-21 水平升高与卒中后 3 个月的 PSCI 相关，而与既定的常规风险因素无关，这表明血浆 FGF-21 在 PSCI 风险分层中可能具有潜在的预后价值。

{"title":"Plasma fibroblast growth factor 21 and risk of cognitive impairment among patients with ischemic stroke","authors":"Xiaowei Zheng , Zhengbao Zhu , Chongke Zhong , Daoxia Guo , Xiaoqing Bu , Hao Peng , Tan Xu , Yonghong Zhang","doi":"10.1016/j.neuroscience.2024.11.012","DOIUrl":"10.1016/j.neuroscience.2024.11.012","url":null,"abstract":"<div><h3>Background and aims</h3><div>Previous study reported that plasma fibroblast growth factor 21 (FGF-21) was associated with poor prognosis in patients with ischemic stroke. The purpose of present study was to prospectively investigate the relationship between plasma FGF-21 and post-stroke cognitive impairment (PSCI).</div></div><div><h3>Methods</h3><div>A total of 600 patients from 7 hospitals were included in this study and plasma FGF-21 levels were examined for all the participants. Cognitive impairment was evaluated using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at 3 months after ischemic stroke onset.</div></div><div><h3>Results</h3><div>323(53.8 %) or 419(69.8 %) participants had PSCI according to MMSE or MoCA at 3 months, respectively. After adjustment for age, National Institutes of Health stroke score, education, and other covariates, the odds ratio of PSCI defined by MMSE and MoCA for the highest vs lowest quartile of plasma FGF-21 was 1.77(1.05–2.98) and 2.40(1.35–4.29), respectively. Multiple-adjusted spline regression model showed a linear association between FGF-21 levels and PSCI (all <em>P</em> < 0.005 for linearity). Subgroup analyses further confirmed these results.</div></div><div><h3>Conclusion</h3><div>Elevated plasma FGF-21 level was associated with PSCI at 3 months after stroke independently of established conventional risk factors, suggesting that plasma FGF-21 may have potential prognostic value in risk stratification of PSCI.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"563 ","pages":"Pages 129-135"},"PeriodicalIF":2.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0