{"title":"慢性酒精暴露会改变成年小鼠海马的肌动蛋白细胞骨架和微管的水平和组装。","authors":"Da-Peng Gao, Lu-Wan Wang, Dong-Lin Xie, Qiong Li, Zhi-Peng Yu, Zi-Hang Tang, Ke-Ke Cui, Yu Cai","doi":"10.31083/j.jin2306118","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Alcohol abuse, a prevalent global health issue, is associated with the onset of cognitive impairment and neurodegeneration. Actin filaments (F-actin) and microtubules (MTs) polymerized from monomeric globular actin (G-actin) and tubulin form the structural basis of the neuronal cytoskeleton. Precise regulation of the assembly and disassembly of these cytoskeletal proteins, and their dynamic balance, play a pivotal role in regulating neuronal morphology and function. Nevertheless, the effect of prolonged alcohol exposure on cytoskeleton dynamics is not fully understood. This study investigates the chronic effects of alcohol on cognitive ability, neuronal morphology and cytoskeleton dynamics in the mouse hippocampus.</p><p><strong>Methods: </strong>Mice were provided <i>ad libitum</i> access to 5% (v/v) alcohol in drinking water and were intragastrically administered 30% (v/v, 6.0 g/kg/day) alcohol for six weeks during adulthood. Cognitive functions were then evaluated using the Y maze, novel object recognition and Morris water maze tests. Hippocampal histomorphology was assessed through hematoxylin-eosin (HE) and Nissl staining. The polymerized and depolymerized states of actin cytoskeleton and microtubules were separated using two commercial assay kits and quantified by Western blot analysis.</p><p><strong>Results: </strong>Mice chronically exposed to alcohol exhibited significant deficits in spatial and recognition memory as evidenced by behavioral tests. Histological analysis revealed notable hippocampal damage and neuronal loss. Decreased ratios of F-actin/G-actin and MT/tubulin, along with reduced levels of polymerized F-actin and MTs, were found in the hippocampus of alcohol-treated mice.</p><p><strong>Conclusions: </strong>Our findings suggest that chronic alcohol consumption disrupted the assembly of the actin cytoskeleton and MTs in the hippocampus, potentially contributing to the cognitive deficits and pathological injury induced by chronic alcohol intoxication.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 6","pages":"118"},"PeriodicalIF":2.5000,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Chronic Alcohol Exposure Alters the Levels and Assembly of the Actin Cytoskeleton and Microtubules in the Adult Mouse Hippocampus.\",\"authors\":\"Da-Peng Gao, Lu-Wan Wang, Dong-Lin Xie, Qiong Li, Zhi-Peng Yu, Zi-Hang Tang, Ke-Ke Cui, Yu Cai\",\"doi\":\"10.31083/j.jin2306118\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Alcohol abuse, a prevalent global health issue, is associated with the onset of cognitive impairment and neurodegeneration. Actin filaments (F-actin) and microtubules (MTs) polymerized from monomeric globular actin (G-actin) and tubulin form the structural basis of the neuronal cytoskeleton. Precise regulation of the assembly and disassembly of these cytoskeletal proteins, and their dynamic balance, play a pivotal role in regulating neuronal morphology and function. Nevertheless, the effect of prolonged alcohol exposure on cytoskeleton dynamics is not fully understood. This study investigates the chronic effects of alcohol on cognitive ability, neuronal morphology and cytoskeleton dynamics in the mouse hippocampus.</p><p><strong>Methods: </strong>Mice were provided <i>ad libitum</i> access to 5% (v/v) alcohol in drinking water and were intragastrically administered 30% (v/v, 6.0 g/kg/day) alcohol for six weeks during adulthood. Cognitive functions were then evaluated using the Y maze, novel object recognition and Morris water maze tests. Hippocampal histomorphology was assessed through hematoxylin-eosin (HE) and Nissl staining. The polymerized and depolymerized states of actin cytoskeleton and microtubules were separated using two commercial assay kits and quantified by Western blot analysis.</p><p><strong>Results: </strong>Mice chronically exposed to alcohol exhibited significant deficits in spatial and recognition memory as evidenced by behavioral tests. Histological analysis revealed notable hippocampal damage and neuronal loss. Decreased ratios of F-actin/G-actin and MT/tubulin, along with reduced levels of polymerized F-actin and MTs, were found in the hippocampus of alcohol-treated mice.</p><p><strong>Conclusions: </strong>Our findings suggest that chronic alcohol consumption disrupted the assembly of the actin cytoskeleton and MTs in the hippocampus, potentially contributing to the cognitive deficits and pathological injury induced by chronic alcohol intoxication.</p>\",\"PeriodicalId\":16160,\"journal\":{\"name\":\"Journal of integrative neuroscience\",\"volume\":\"23 6\",\"pages\":\"118\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-06-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of integrative neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.31083/j.jin2306118\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of integrative neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.31083/j.jin2306118","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
背景:酗酒是一个普遍的全球性健康问题,它与认知障碍和神经变性的发生有关。由单体球状肌动蛋白(G-actin)和微管蛋白聚合而成的肌动蛋白丝(F-actin)和微管(MT)构成了神经元细胞骨架的结构基础。精确调节这些细胞骨架蛋白的组装和分解及其动态平衡,在调节神经元形态和功能方面起着关键作用。然而,长期暴露于酒精对细胞骨架动力学的影响尚未完全明了。本研究探讨了酒精对小鼠海马认知能力、神经元形态和细胞骨架动力学的长期影响:方法:小鼠成年后可自由饮用含 5%(v/v)酒精的饮用水,并在胃内注射 30%(v/v,6.0 克/千克/天)酒精,为期六周。然后使用Y迷宫、新物体识别和莫里斯水迷宫测试评估认知功能。海马组织形态学通过苏木精-伊红(HE)和 Nissl 染色进行评估。使用两种商业检测试剂盒分离肌动蛋白细胞骨架和微管的聚合和解聚状态,并通过 Western 印迹分析进行量化:结果:长期暴露于酒精的小鼠在行为测试中表现出明显的空间记忆和识别记忆缺陷。组织学分析表明,海马受损和神经元丢失明显。在经酒精处理的小鼠海马中发现,F-肌动蛋白/G-肌动蛋白和MT/微管蛋白的比率下降,聚合的F-肌动蛋白和MT水平降低:我们的研究结果表明,长期饮酒会破坏海马中肌动蛋白细胞骨架和MTs的组装,从而可能导致慢性酒精中毒引起的认知障碍和病理损伤。
Chronic Alcohol Exposure Alters the Levels and Assembly of the Actin Cytoskeleton and Microtubules in the Adult Mouse Hippocampus.
Background: Alcohol abuse, a prevalent global health issue, is associated with the onset of cognitive impairment and neurodegeneration. Actin filaments (F-actin) and microtubules (MTs) polymerized from monomeric globular actin (G-actin) and tubulin form the structural basis of the neuronal cytoskeleton. Precise regulation of the assembly and disassembly of these cytoskeletal proteins, and their dynamic balance, play a pivotal role in regulating neuronal morphology and function. Nevertheless, the effect of prolonged alcohol exposure on cytoskeleton dynamics is not fully understood. This study investigates the chronic effects of alcohol on cognitive ability, neuronal morphology and cytoskeleton dynamics in the mouse hippocampus.
Methods: Mice were provided ad libitum access to 5% (v/v) alcohol in drinking water and were intragastrically administered 30% (v/v, 6.0 g/kg/day) alcohol for six weeks during adulthood. Cognitive functions were then evaluated using the Y maze, novel object recognition and Morris water maze tests. Hippocampal histomorphology was assessed through hematoxylin-eosin (HE) and Nissl staining. The polymerized and depolymerized states of actin cytoskeleton and microtubules were separated using two commercial assay kits and quantified by Western blot analysis.
Results: Mice chronically exposed to alcohol exhibited significant deficits in spatial and recognition memory as evidenced by behavioral tests. Histological analysis revealed notable hippocampal damage and neuronal loss. Decreased ratios of F-actin/G-actin and MT/tubulin, along with reduced levels of polymerized F-actin and MTs, were found in the hippocampus of alcohol-treated mice.
Conclusions: Our findings suggest that chronic alcohol consumption disrupted the assembly of the actin cytoskeleton and MTs in the hippocampus, potentially contributing to the cognitive deficits and pathological injury induced by chronic alcohol intoxication.
期刊介绍:
JIN is an international peer-reviewed, open access journal. JIN publishes leading-edge research at the interface of theoretical and experimental neuroscience, focusing across hierarchical levels of brain organization to better understand how diverse functions are integrated. We encourage submissions from scientists of all specialties that relate to brain functioning.