Reitz Nicole L, Nunes Polliana T, Savage Lisa M
Department of Psychology, Binghamton University, State University of New York, Binghamton, NY, United States.
Front Behav Neurosci. 2024 Aug 1;18:1448691. doi: 10.3389/fnbeh.2024.1448691. eCollection 2024.
Human 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.
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.
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.
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.
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）更早发病，尤其是在具有AD遗传易感性的个体中。在关键发育时间点，如青春期，与酒精相关的脑损伤（ARBD）会与AD相关病理相互作用，加速晚年疾病进展。本研究调查成年中期的自愿运动是否能恢复由青春期乙醇暴露与AD转基因相互作用引起的记忆缺陷。
雄性和雌性TgF344-AD大鼠和野生型F344大鼠在整个青春期（出生后第27 - 57天）接受为期2天开/关方案的胃内灌胃，灌胃液体为水（对照）或5 g/kg的20%乙醇（青春期间歇性乙醇；AIE）。6个月大时，大鼠要么留在笼中（静止），要么被置于自愿轮转跑步装置中4周，然后进行多项行为测试。评估基底前脑胆碱能神经元数量以及海马体中的神经发生情况。
自愿轮转跑步选择性地恢复了暴露于AIE的雌性TgF344-AD大鼠的空间工作记忆缺陷，并改善了对照TgF344-AD雌性大鼠中出现的模式分离损伤。对脑病理存在性别依赖性影响：运动改善了暴露于AIE的TgF344-AD雌性大鼠中新生神经元的整合。运动导致海马体和内嗅皮质中淀粉样蛋白负荷减少，但仅在暴露于AIE的雄性TgF344-AD大鼠中出现这种情况。虽然基底前脑胆碱能神经元数量在两性中均不受AD转基因影响，但AIE确实减少了雌性大鼠基底前脑胆碱能神经元数量。
这些数据支持，即使在症状出现后，AIE和AD相关的认知衰退及相关神经病理可以通过运动以独特的性别特异性方式得到挽救。
