School of Physical Education, Xizang Minzu University, Xianyang, China.
School of Physical Education & Health Care, East China Normal University, Shanghai, China.
Neurosci Lett. 2019 May 14;701:84-91. doi: 10.1016/j.neulet.2019.02.030. Epub 2019 Feb 20.
Mitochondrial dysfunction is widely recognized as an early event in the pathogenesis of Alzheimer's disease (AD). Defects in mitochondrial fusion and fission have been proposed to lead to learning and memory impairments in AD. The current study aimed to investigate whether exercise-improved learning and memory were associated with improves in mitochondrial function by increased mitochondrial fusion and decreased mitochondrial fission. APP/PS1 transgenic mice were divided into transgenic sedentary (ADC, n = 15) and transgenic exercise (ADE, n = 15) groups. Wild-type mice were also separated into sedentary (WTC, n = 15) and exercise (WTE, n = 15) groups. The WTE and ADE mice were subjected to treadmill exercise for 12 weeks. In this study, learning and memory were significantly decreased in ADC mice compared with those in WTC mice, whereas exercise improved learning and memory in APP/PS1 transgenic mice. Meanwhile, ADC mice displayed defective mitochondrial function as evidenced by a significant increase in swollen mitochondria and vacuoles, loss of mitochondrial cristae, and decreased ATP levels, as well as an imbalance in mitochondrial fusion and fission as evidenced by significantly increased Drp1 and Mff and decreased Mfn1, Mfn2, and Opa1 in the hippocampus. Interestingly, exercise mitigated mitochondrial dysfunction as evidenced by a significant reduction in swollen mitochondria and vacuoles and increased mitochondrial cristae and ATP levels in ADE mice. Coincidentally, exercise promoted the balance of mitochondrial fusion and fission as evidenced by a significantly decreased Drp1 and Mff and increased Mfn1, Mfn2, and Opa1 in the hippocampus. These findings suggest that treadmill exercise efficiently enhances learning and memory in AD by improving mitochondrial dysfunction in APP/PS1 transgenic mice.
线粒体功能障碍被广泛认为是阿尔茨海默病（AD）发病机制中的早期事件。线粒体融合和裂变缺陷被认为导致 AD 中的学习和记忆损伤。本研究旨在通过增加线粒体融合和减少线粒体裂变来研究运动改善学习和记忆是否与改善线粒体功能有关。APP/PS1 转基因小鼠分为转基因久坐（ADC，n = 15）和转基因运动（ADE，n = 15）组。野生型小鼠也分为久坐（WTC，n = 15）和运动（WTE，n = 15）组。WTE 和 ADE 小鼠进行了 12 周的跑步机运动。在这项研究中，与 WTC 小鼠相比，ADC 小鼠的学习和记忆能力明显下降，而运动改善了 APP/PS1 转基因小鼠的学习和记忆能力。同时，ADC 小鼠表现出线粒体功能缺陷，表现为线粒体肿胀和空泡增加，线粒体嵴丢失，ATP 水平降低，以及线粒体融合和裂变失衡，表现为 Drp1 和 Mff 显著增加，而 Mfn1、Mfn2 和 Opa1 减少在海马体中。有趣的是，运动减轻了线粒体功能障碍，表现为 ADE 小鼠的肿胀线粒体和空泡减少，线粒体嵴增加，ATP 水平升高。巧合的是，运动促进了线粒体融合和裂变的平衡，表现为 Drp1 和 Mff 显著降低，而 Mfn1、Mfn2 和 Opa1 在海马体中增加。这些发现表明，跑步机运动通过改善 APP/PS1 转基因小鼠的线粒体功能障碍，有效地提高了 AD 中的学习和记忆能力。
