College of Sports and Human Sciences, Harbin Sport University, 150008 Harbin, Heilongjiang, China.
Department of Exercise Physiology, Beijing Sport University, 100084 Beijing, China.
J Integr Neurosci. 2024 Jul 23;23(7):136. doi: 10.31083/j.jin2307136.
Physical exercise has been shown to be beneficial for individuals with Alzheimer's disease (AD), although the underlying mechanisms are not fully understood.
Six-month-old Amyloid precursor protein/Presenilin 1 (APP/PS1) transgenic (Tg) mice and wild-type (Wt) mice were randomly assigned to either a sedentary group (Tg-Sed, Wt-Sed) or an exercise group (Tg-Ex, Wt-Ex) undertaking a 12-week, moderate-intensity treadmill running program. Consequently, all mice were tested for memory function and amyloid β (Aβ) levels and phosphorylation of tau and protein kinase B (Akt)/glycogen synthase kinase-3 (GSK3) were examined in tissues of both the cortex and hippocampus.
Tg-Sed mice had severely impaired memory, higher levels of Aβ, and increased phosphorylation of tau, GSK3α tyrosine279, and GSK3β tyrosine216, but less phosphorylation of GSK3α serine21, GSK3β serine9, and Akt serine473 in both tissues than Wt-Sed mice in respective tissues. Tg-Ex mice showed significant improvement in memory function along with lower levels of Aβ and less phosphorylation of tau (both tissues), GSK3α tyrosine279 (both tissues), and GSK3β tyrosine216 (hippocampus only), but increased phosphorylation of GSK3α serine21 (both tissues), GSK3β serine9 (hippocampus only), and Akt serine473 (both tissues) compared with Tg-Sed mice in respective tissues.
Moderate-intensity aerobic exercise is highly effective in improving memory function in 9-month-old APP/PS1 mice, most likely through differential modulation of GSK3α/β phosphorylation in the cortex and hippocampus.
运动已被证明对阿尔茨海默病（AD）患者有益，尽管其潜在机制尚不完全清楚。
将 6 月龄 APP/PS1 转基因（Tg）小鼠和野生型（Wt）小鼠随机分为久坐组（Tg-Sed，Wt-Sed）和运动组（Tg-Ex，Wt-Ex），进行为期 12 周的中等强度跑步机跑步运动。然后对所有小鼠进行记忆功能和淀粉样β（Aβ）水平检测，并检测大脑皮质和海马组织中 tau 和蛋白激酶 B（Akt）/糖原合成酶激酶 3（GSK3）的磷酸化。
Tg-Sed 小鼠记忆功能严重受损，Aβ水平升高，tau、GSK3α 酪氨酸 279 和 GSK3β 酪氨酸 216 磷酸化增加，但大脑皮质和海马组织中 GSK3α 丝氨酸 21、GSK3β 丝氨酸 9 和 Akt 丝氨酸 473 的磷酸化减少。Tg-Ex 小鼠记忆功能明显改善，Aβ水平降低，tau（大脑皮质和海马组织）、GSK3α 酪氨酸 279（大脑皮质和海马组织）和 GSK3β 酪氨酸 216（仅海马组织）磷酸化减少，但 GSK3α 丝氨酸 21（大脑皮质和海马组织）、GSK3β 丝氨酸 9（仅海马组织）和 Akt 丝氨酸 473（大脑皮质和海马组织）的磷酸化增加。
中等强度有氧运动能显著改善 9 月龄 APP/PS1 小鼠的记忆功能，这可能与大脑皮质和海马组织中 GSK3α/β 磷酸化的差异调节有关。
