Amyloid beta (Aβ), one of the main hallmarks of Alzheimer’s Disease (AD), may stimulate pattern recognition receptors (PRR) such as the NLRP3 inflammasome, inducing a pro-inflammatory state in the brain that contributes to disease development. Physical exercise can have multiple beneficial effects on brain function, including anti-inflammatory and neuroprotective roles. The objective of this study was to investigate the prophylactic effect of moderate treadmill exercise for 4 weeks on inflammatory events related to NLRP3 signaling in the hippocampus of mice after intracerebroventricular Aβ₁₋₄₀ administration. Our results show that Aβ₁₋₄₀ administration (400 pmol/mouse, i.c.v.) significantly increased the immunocontent Iba-1 (a microglial reactivity marker), NLRP3, TXNIP, and caspase-1 in the hippocampus of mice. However, physical exercise prevented the hippocampal increase in Iba-1, TXNIP, and activation of the NLRP3 inflammasome pathway caused by Aβ₁₋₄₀. Moreover, physical exercise per se reduced the TXNIP and caspase-1 immunocontent in the hippocampus. No alterations were observed on the immunocontent of GFAP, ASC, and IL-1β in the hippocampus after Aβ₁₋₄₀ and/or physical exercise. These results reinforce the role of NLRP3 inflammasome pathway in AD and point to physical exercise as a possible non-pharmacological strategy to prevent inflammatory events triggered by Aβ₁₋₄₀ in mice.

淀粉样蛋白 β (Aβ) 是阿尔茨海默病 (AD) 的主要标志之一，它可能会刺激模式识别受体 (PRR)，例如 NLRP3 炎症小体，从而在大脑中诱导促炎状态，从而促进疾病的发展。体育锻炼可以对大脑功能产生多种有益影响，包括抗炎和神经保护作用。本研究的目的是研究 4 周适度跑步机运动对脑室内 Aβ _1-40给药后小鼠海马中与 NLRP3 信号传导相关的炎症事件的预防作用。我们的结果表明 Aβ ₁₋₄₀给药 (400 pmol/mouse, icv) 显着增加了小鼠海马中的免疫含量 Iba-1（小胶质细胞反应性标记物）、NLRP3、TXNIP 和 caspase-1。然而，体育锻炼阻止了海马区 Iba-1、TXNIP 的增加以及由 Aβ _1-40引起的 NLRP3 炎性体通路的激活。此外，体育锻炼本身降低了海马中的 TXNIP 和 caspase-1 免疫含量。在 Aβ _1-40和/或体育锻炼后，海马中 GFAP、ASC 和 IL-1β 的免疫含量未观察到变化。这些结果强化了 NLRP3 炎症小体通路在 AD 中的作用，并指出体育锻炼是预防由 Aβ _1-40引发的炎症事件的一种可能的非药物策略 在老鼠身上。