Prophylactic effect of physical exercise on Aβ1-40-induced depressive-like behavior and gut dysfunction in mice

• Published in: Behavioural brain research 2020-09, Vol.393, p.112791-112791, Article 112791
• Main Authors: Rosa, Julia M., Pazini, Francis L., Camargo, Anderson, Wolin, Ingrid A.V., Olescowicz, Gislaine, Eslabão, Livia B., Romero, Oscar Bruna, Winkelmann-Duarte, Elisa C., S. Rodrigues, Ana Lúcia
• Format: Article
• Language: English
• Subjects: Alzheimer’s disease; Amyloid β1-40 peptide; Intestine; Microbiota; Physical exercise
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2020.112791

•Exercise prevented Aβ1–40-induced depressive-like behavior.•Exercise increased villus width and height in the duodenum.•Exercise raised Goblet cells and Paneth cells in the duodenum.•Exercise abolished duodenal ultrastructural changes induced by Aβ1–40.•Exercise prevented Aβ1–40-induced alterations in fecal microbiota composition. 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 β1-40 peptide (Aβ1-40)-induced depressive-like behavior, alterations in morphological parameters of the duodenum, and the abundance of Firmicutes and Bacteroidetes phyla. Aβ1-40 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 Aβ1-40-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, Aβ1-40 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 Aβ1-40-exposed mice were prevented by the practice of physical exercise. Altogether the results provide evidence of the prophylactic effect of physical exercise on Aβ1-40-induced depressive-like behavior and gut dysfunction in mice, suggesting that physical exercise could be useful for preventing depression associated with AD.