UNASSIGNED: Male 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.
UNASSIGNED: Voluntary 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.
UNASSIGNED: These 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.
■雄性和雌性TgF344-AD和野生型F344大鼠在整个青春期暴露于胃内管饲的水(对照)或5g/kg的20%乙醇(青春期间歇性乙醇;AIE)2天的开/关时间表(PD27-57)。在6个月大的时候,大鼠要么留在笼子里(静止),要么放在自愿的车轮运行设备中4周,然后进行几次行为测试。评估了基底前脑中胆碱能神经元的数量以及海马中神经发生的测量。
■在暴露于AIE的雌性TgF344-AD大鼠中,自愿轮跑步选择性地恢复了空间工作记忆缺陷,并改善了在对照TgF344-AD雌性大鼠中观察到的模式分离障碍。对大脑病理学有性别依赖性影响:运动可改善暴露于AIE的TgF344-AD雌性大鼠中最近出生的神经元的整合。运动导致海马和内嗅皮层的淀粉样蛋白负荷减少,但只在雄性AIE暴露的TgF344-AD大鼠中。尽管基底前脑胆碱能神经元的数量不受任何性别的AD转基因的影响,AIE确实减少了雌性大鼠基底前脑胆碱能神经元的数量。
■这些数据提供了支持,即使在症状发作后,AIE和AD相关的认知下降和相关的神经病理学可以通过运动以独特的性别特异性方式来挽救。