School of Health and Kinesiology, University of Nebraska at Omaha, Omaha, Nebraska.
Department of Physiology, College of Medicine, KyungHee University, Seoul, Republic of Korea.
J Appl Physiol (1985). 2022 Apr 1;132(4):1054-1068. doi: 10.1152/japplphysiol.00751.2021. Epub 2022 Feb 24.
Alzheimer's disease (AD) is a progressive degenerative brain disease and the primary cause of dementia. At an early stage, AD is generally characterized by short-term memory impairment, owing to dysfunctions of the cortex and hippocampus. We previously reported that a combination of exercise and 40-Hz light flickering can protect against AD-related neuroinflammation, gamma oscillations, reduction in Aβ, and cognitive decline. Therefore, we sought to extend our previous findings to the 5-mo-old 3×Tg-AD mouse model to examine whether the same favorable effects occur in earlier stages of cognitive dysfunction. We investigated the effects of 12 wk of exercise combined with 40-Hz light flickering on cognitive function by analyzing neuroinflammation, mitochondrial function, and neuroplasticity in the hippocampus in a 3×Tg-AD mouse model. Five-month-old 3×Tg-AD mice performed 12 wk of exercise with 40-Hz light flickering administered independently and in combination. Spatial learning and memory, long-term memory, hippocampal Aβ, tau, neuroinflammation, proinflammatory cytokine expression, mitochondrial function, and neuroplasticity were analyzed. Aβ and tau proteins levels were significantly reduced in the early stage of AD, resulting in protection against cognitive decline by reducing neuroinflammation and proinflammatory cytokines. Furthermore, mitochondrial function improved, apoptosis was reduced, and synapse-related protein expression increased. Overall, exercise with 40-Hz light flickering was significantly more effective than exercise or 40-Hz light flickering alone, and the improvement was comparable to the levels in the nontransgenic aged-match control group. Our results indicate a synergistic effect of exercise and 40-Hz light flickering on pathological improvements in the hippocampus during early AD-associated cognitive impairment. Exercising in a 40-Hz light flicker environment was more effective than exercise or 40-Hz light flicker alone. This synergistic effect may prevent cognitive dysfunction by inhibiting Aβ, tau pathway, and neuroinflammation and enhancing neuroplasticity and mitochondrial functions in the hippocampus during early Alzheimer's disease.
阿尔茨海默病（AD）是一种进行性退行性脑疾病，也是痴呆的主要病因。在早期，AD 通常表现为短期记忆障碍，这归因于皮质和海马体的功能障碍。我们之前的研究表明，运动与 40Hz 光闪烁的结合可以预防 AD 相关的神经炎症、γ 振荡、Aβ 的减少和认知能力下降。因此，我们试图将之前的研究结果扩展到 5 月龄的 3×Tg-AD 小鼠模型，以研究相同的有利效果是否发生在认知功能障碍的早期阶段。我们通过分析海马体中的神经炎症、线粒体功能和神经可塑性，研究了 12 周的运动与 40Hz 光闪烁联合应用对 3×Tg-AD 小鼠模型认知功能的影响。5 月龄的 3×Tg-AD 小鼠进行了 12 周的运动与 40Hz 光闪烁的联合应用，或独立应用。分析了空间学习和记忆、长时记忆、海马体 Aβ、tau、神经炎症、促炎细胞因子表达、线粒体功能和神经可塑性。AD 早期 Aβ和 tau 蛋白水平显著降低，通过减少神经炎症和促炎细胞因子来保护认知能力免受下降。此外，线粒体功能得到改善，凋亡减少，突触相关蛋白表达增加。总的来说，运动与 40Hz 光闪烁的联合应用比运动或 40Hz 光闪烁单独应用更有效，改善效果与非转基因年龄匹配对照组相当。我们的研究结果表明，在早期 AD 相关认知障碍期间，运动与 40Hz 光闪烁对海马体的病理改善具有协同作用。在 40Hz 光闪烁环境中运动比单独运动或 40Hz 光闪烁更有效。这种协同作用可能通过抑制 Aβ、tau 通路和神经炎症，增强海马体的神经可塑性和线粒体功能，预防认知功能障碍。
