前沿| 在TgF344-AD模型中，青少年暴露于乙醇后，运动可导致行为和病理性AD标记物的性别特异性恢复

IF 2.6 3区医学 Q2 BEHAVIORAL SCIENCES

Frontiers in Behavioral Neuroscience Pub Date : 2024-07-12 DOI:10.3389/fnbeh.2024.1448691

Nicole L. Reitz, Polliana T. Nunes, Lisa M. Savage

{"title":"前沿| 在TgF344-AD模型中，青少年暴露于乙醇后，运动可导致行为和病理性AD标记物的性别特异性恢复","authors":"Nicole L. Reitz, Polliana T. Nunes, Lisa M. Savage","doi":"10.3389/fnbeh.2024.1448691","DOIUrl":null,"url":null,"abstract":"IntroductionHuman epidemiological studies suggest that heavy alcohol consumption may lead to earlier onset of Alzheimer’s Disease (AD), especially in individuals with a genetic predisposition for AD. Alcohol-related brain damage (ARBD) during a critical developmental timepoint, such as adolescence, interacts with AD-related pathologies to accelerate disease progression later in life. The current study investigates if voluntary exercise in mid-adulthood can recover memory deficits caused by the interactions between adolescence ethanol exposure and AD-transgenes.MethodsMale and female TgF344-AD and wildtype F344 rats were exposed to an intragastric gavage of water (control) or 5 g/kg of 20% ethanol (adolescent intermittent ethanol; AIE) for a 2 day on/off schedule throughout adolescence (PD27-57). At 6 months old, rats either remained in their home cage (stationary) or were placed in a voluntary wheel running apparatus for 4 weeks and then underwent several behavioral tests. The number of cholinergic neurons in the basal forebrain and measure of neurogenesis in the hippocampus were assessed.ResultsVoluntary wheel running recovers spatial working memory deficits selectively in female TgF344-AD rats exposed to AIE and improves pattern separation impairment seen in control TgF344-AD female rats. There were sex-dependent effects on brain pathology: Exercise improves the integration of recently born neurons in AIE-exposed TgF344-AD female rats. Exercise led to a decrease in amyloid burden in the hippocampus and entorhinal cortex, but only in male AIE-exposed TgF344-AD rats. Although the number of basal forebrain cholinergic neurons was not affected by AD-transgenes in either sex, AIE did reduce the number of basal forebrain cholinergic neurons in female rats.DiscussionThese data provide support that even after symptom onset, AIE and AD related cognitive decline and associated neuropathologies can be rescued with exercise in unique sex-specific ways.","PeriodicalId":12368,"journal":{"name":"Frontiers in Behavioral Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Frontiers | Exercise leads to sex-specific recovery of behavior and pathological AD markers following adolescent ethanol exposure in the TgF344-AD model\",\"authors\":\"Nicole L. Reitz, Polliana T. Nunes, Lisa M. Savage\",\"doi\":\"10.3389/fnbeh.2024.1448691\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"IntroductionHuman epidemiological studies suggest that heavy alcohol consumption may lead to earlier onset of Alzheimer’s Disease (AD), especially in individuals with a genetic predisposition for AD. Alcohol-related brain damage (ARBD) during a critical developmental timepoint, such as adolescence, interacts with AD-related pathologies to accelerate disease progression later in life. The current study investigates if voluntary exercise in mid-adulthood can recover memory deficits caused by the interactions between adolescence ethanol exposure and AD-transgenes.MethodsMale and female TgF344-AD and wildtype F344 rats were exposed to an intragastric gavage of water (control) or 5 g/kg of 20% ethanol (adolescent intermittent ethanol; AIE) for a 2 day on/off schedule throughout adolescence (PD27-57). At 6 months old, rats either remained in their home cage (stationary) or were placed in a voluntary wheel running apparatus for 4 weeks and then underwent several behavioral tests. The number of cholinergic neurons in the basal forebrain and measure of neurogenesis in the hippocampus were assessed.ResultsVoluntary wheel running recovers spatial working memory deficits selectively in female TgF344-AD rats exposed to AIE and improves pattern separation impairment seen in control TgF344-AD female rats. There were sex-dependent effects on brain pathology: Exercise improves the integration of recently born neurons in AIE-exposed TgF344-AD female rats. Exercise led to a decrease in amyloid burden in the hippocampus and entorhinal cortex, but only in male AIE-exposed TgF344-AD rats. Although the number of basal forebrain cholinergic neurons was not affected by AD-transgenes in either sex, AIE did reduce the number of basal forebrain cholinergic neurons in female rats.DiscussionThese data provide support that even after symptom onset, AIE and AD related cognitive decline and associated neuropathologies can be rescued with exercise in unique sex-specific ways.\",\"PeriodicalId\":12368,\"journal\":{\"name\":\"Frontiers in Behavioral Neuroscience\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-07-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Behavioral Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fnbeh.2024.1448691\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BEHAVIORAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Behavioral Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fnbeh.2024.1448691","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}

引用次数: 0

摘要

导言：人类流行病学研究表明，大量饮酒可能会导致阿尔茨海默病（AD）提前发病，尤其是在具有阿尔茨海默病遗传倾向的个体中。在青春期等关键发育时间点，与酒精相关的脑损伤（ARBD）会与阿氏痴呆症相关的病理变化相互作用，从而加速后期的疾病进展。方法在整个青春期（PD27-57），雄性和雌性TgF344-AD大鼠及野生型F344大鼠被灌胃水（对照组）或5克/千克的20%乙醇（青春期间歇性乙醇；AIE），持续2天。6 个月大时，大鼠要么呆在家中的笼子里（静止），要么被置于自愿轮跑装置中 4 周，然后接受多项行为测试。结果自愿轮跑可选择性地恢复暴露于AIE的TgF344-AD雌性大鼠的空间工作记忆缺陷，并改善对照组TgF344-AD雌性大鼠的模式分离障碍。对大脑病理学的影响与性别有关：在暴露于 AIE 的 TgF344-AD 雌性大鼠中，运动可改善新出生神经元的整合。运动可减少海马和内侧皮层的淀粉样蛋白负荷，但只有雄性暴露于AIE的TgF344-AD大鼠才会出现这种情况。虽然雌雄大鼠基底前脑胆碱能神经元的数量都不受AD转基因的影响，但AIE确实减少了雌性大鼠基底前脑胆碱能神经元的数量。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Frontiers | Exercise leads to sex-specific recovery of behavior and pathological AD markers following adolescent ethanol exposure in the TgF344-AD model

IntroductionHuman epidemiological studies suggest that heavy alcohol consumption may lead to earlier onset of Alzheimer’s Disease (AD), especially in individuals with a genetic predisposition for AD. Alcohol-related brain damage (ARBD) during a critical developmental timepoint, such as adolescence, interacts with AD-related pathologies to accelerate disease progression later in life. The current study investigates if voluntary exercise in mid-adulthood can recover memory deficits caused by the interactions between adolescence ethanol exposure and AD-transgenes.MethodsMale and female TgF344-AD and wildtype F344 rats were exposed to an intragastric gavage of water (control) or 5 g/kg of 20% ethanol (adolescent intermittent ethanol; AIE) for a 2 day on/off schedule throughout adolescence (PD27-57). At 6 months old, rats either remained in their home cage (stationary) or were placed in a voluntary wheel running apparatus for 4 weeks and then underwent several behavioral tests. The number of cholinergic neurons in the basal forebrain and measure of neurogenesis in the hippocampus were assessed.ResultsVoluntary wheel running recovers spatial working memory deficits selectively in female TgF344-AD rats exposed to AIE and improves pattern separation impairment seen in control TgF344-AD female rats. There were sex-dependent effects on brain pathology: Exercise improves the integration of recently born neurons in AIE-exposed TgF344-AD female rats. Exercise led to a decrease in amyloid burden in the hippocampus and entorhinal cortex, but only in male AIE-exposed TgF344-AD rats. Although the number of basal forebrain cholinergic neurons was not affected by AD-transgenes in either sex, AIE did reduce the number of basal forebrain cholinergic neurons in female rats.DiscussionThese data provide support that even after symptom onset, AIE and AD related cognitive decline and associated neuropathologies can be rescued with exercise in unique sex-specific ways.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Frontiers in Behavioral Neuroscience BEHAVIORAL SCIENCES-NEUROSCIENCES

CiteScore

4.70

自引率

3.30%

发文量

506

审稿时长

6-12 weeks

期刊介绍： Frontiers in Behavioral Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the neural mechanisms underlying behavior. Field Chief Editor Nuno Sousa at the Instituto de Pesquisa em Ciências da Vida e da Saúde (ICVS) is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. This journal publishes major insights into the neural mechanisms of animal and human behavior, and welcomes articles studying the interplay between behavior and its neurobiological basis at all levels: from molecular biology and genetics, to morphological, biochemical, neurochemical, electrophysiological, neuroendocrine, pharmacological, and neuroimaging studies.