Department of Physical Education and Sport Sciences, Faculty of Humanities, Tarbiat Modares University, Tehran, Iran.
Department of Physical Education and Sport Sciences, Faculty of Humanities, Tarbiat Modares University, Tehran, Iran.
Peptides. 2018 Apr;102:78-88. doi: 10.1016/j.peptides.2017.12.027. Epub 2018 Jan 5.
Alzheimer's disease (AD) is a neurodegenerative disorder associated with loss of memory and cognitive abilities. Previous evidence suggested that exercise ameliorates learning and memory deficits by increasing brain derived neurotrophic factor (BDNF) and activating downstream pathways in AD animal models. However, upstream pathways related to increase BDNF induced by exercise in AD animal models are not well known. We investigated the effects of moderate treadmill exercise on Aβ-induced learning and memory impairment as well as the upstream pathway responsible for increasing hippocampal BDNF in an animal model of AD. Animals were divided into five groups: Intact, Sham, Aβ, Sham-exercise (Sham-exe) and Aβ-exercise (Aβ-exe). Aβ was microinjected into the CA1 area of the hippocampus and then animals in the exercise groups were subjected to moderate treadmill exercise (for 4 weeks with 5 sessions per week) 7 days after microinjection. In the present study the Morris water maze (MWM) test was used to assess spatial learning and memory. Hippocampal mRNA levels of BDNF, peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), fibronectin type III domain-containing 5 (FNDC5) as well as protein levels of AMPK-activated protein kinase (AMPK), PGC-1α, BDNF, phosphorylation of AMPK were measured. Our results showed that intra-hippocampal injection of Aβ impaired spatial learning and memory which was accompanied by reduced AMPK activity (p-AMPK/total-AMPK ratio) and suppression of the PGC-1α/FNDC5/BDNF pathway in the hippocampus of rats. In contrast, moderate treadmill exercise ameliorated the Aβ-induced spatial learning and memory deficit, which was accompanied by restored AMPK activity and PGC-1α/FNDC5/BDNF levels. Our results suggest that the increased AMPK activity and up-regulation of the PGC-1α/FNDC5/BDNF pathway by exercise are likely involved in mediating the beneficial effects of exercise on Aβ-induced learning and memory impairment.
阿尔茨海默病（AD）是一种与记忆和认知能力丧失相关的神经退行性疾病。先前的证据表明，运动通过增加脑源性神经营养因子（BDNF）并激活 AD 动物模型中的下游途径来改善学习和记忆缺陷。然而，运动在 AD 动物模型中引起 BDNF 增加的上游途径尚不清楚。我们研究了中度跑步机运动对 Aβ诱导的学习和记忆障碍的影响，以及负责增加 AD 动物模型中海马 BDNF 的上游途径。动物分为五组：完整组、假手术组、Aβ 组、假手术运动组（Sham-exe）和 Aβ 运动组（Aβ-exe）。Aβ 被微注射到海马 CA1 区，然后在微注射后 7 天，运动组动物接受中度跑步机运动（4 周，每周 5 次）。在本研究中，使用 Morris 水迷宫（MWM）测试评估空间学习和记忆。测量了海马 BDNF、过氧化物酶体增殖物激活受体γ共激活因子 1α（PGC-1α）、纤维连接蛋白 III 结构域包含 5（FNDC5）的 mRNA 水平以及 AMPK 激活的蛋白激酶（AMPK）、PGC-1α、BDNF、AMPK 磷酸化的蛋白水平。我们的结果表明，海马内注射 Aβ 损害了空间学习和记忆，这伴随着 AMPK 活性的降低（p-AMPK/总-AMPK 比值）和海马中 PGC-1α/FNDC5/BDNF 途径的抑制。相反，中度跑步机运动改善了 Aβ 诱导的空间学习和记忆缺陷，这伴随着 AMPK 活性的恢复和 PGC-1α/FNDC5/BDNF 水平的升高。我们的结果表明，运动引起的 AMPK 活性增加和 PGC-1α/FNDC5/BDNF 途径的上调可能参与介导运动对 Aβ 诱导的学习和记忆障碍的有益作用。
