Alzheimer's disease (AD) is a prevalent neurodegenerative disease that is highly comorbid with depression. Gut dysfunction has been proposed as a possible risk factor for both clinical conditions. In the present study, we investigated the ability of treadmill exercise for 4 weeks (5 days/week, 40 min/day) to counteract amyloid β_1-40 peptide (Aβ_1-40)-induced depressive-like behavior, alterations in morphological parameters of the duodenum, and the abundance of Firmicutes and Bacteroidetes phyla. Aβ_1-40 administration (400 pmol/mouse, i.c.v.) increased immobility time in the tail suspension test (TST) and reduced time spent sniffing in the female urine sniffing test (FUST), indicating behavioral despair and impairment in reward-seeking behavior. These behavioral alterations, indicative of depressive-like behavior, were accompanied by reduced villus width in the duodenum. Moreover, photomicrographs obtained by transmission electron microscopy revealed abnormal epithelial microvilli in the duodenum from sedentary Aβ_1-40-exposed mice, characterized by shorter microvilli and heterogeneity in the length of these structures that exhibit a disordered packing. Regarding the ultrastructure of Paneth cells, Aβ_1-40 administration caused a reduction in the secretory granule diameter, as well as an enlarged peripheral halo. These animals also presented reduced Firmicutes and increased Bacteroidetes abundance, and increased Bacteroidetes/Firmicutes ratio. Most of the alterations observed in Aβ_1-40-exposed mice were prevented by the practice of physical exercise. Altogether the results provide evidence of the prophylactic effect of physical exercise on Aβ_1-40-induced depressive-like behavior and gut dysfunction in mice, suggesting that physical exercise could be useful for preventing depression associated with AD.

阿尔茨海默病 (AD) 是一种普遍存在的神经退行性疾病，与抑郁症高度共存。肠道功能障碍被认为是这两种临床状况的可能危险因素。在本研究中，我们调查了跑步机运动 4 周（5 天/周，40 分钟/天）对抗淀粉样蛋白 β _1-40肽（Aβ _1-40）诱导的抑郁样行为、形态学改变的能力十二指肠的参数，以及厚壁菌门和拟杆菌门的丰度。Aβ _1-40给药（400 pmol/小鼠，icv）增加了悬尾试验（TST）中的不动时间，减少了雌性尿液嗅探试验（FUST）中的嗅探时间，表明行为绝望和寻求奖励行为受损。这些表现出抑郁样行为的行为改变伴随着十二指肠绒毛宽度的减少。此外，通过透射电子显微镜获得的显微照片显示，久坐的 Aβ _1-40暴露小鼠的十二指肠上皮微绒毛异常，其特征是微绒毛较短，这些结构的长度不均匀，表现出无序排列。关于潘氏细胞的超微结构，Aβ _1-40给药导致分泌颗粒直径减小以及外周晕圈扩大。这些动物还表现出厚壁菌门减少和拟杆菌门丰度增加，以及拟杆菌门/厚壁菌门比率增加。在暴露于 Aβ _{1-40 的}小鼠中观察到的大部分变化都可以通过体育锻炼来防止。总之，这些结果提供了体育锻炼对 Aβ _1-40诱导的小鼠抑郁样行为和肠道功能障碍的预防作用的证据，表明体育锻炼可用于预防与 AD 相关的抑郁症。