Abstract：
BACKGROUND: Physical exercise has been shown to be beneficial for individuals with Alzheimer\'s disease (AD), although the underlying mechanisms are not fully understood.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：体育锻炼已被证明对阿尔茨海默病（AD）患者有益，尽管潜在的机制还没有完全理解。
方法：将六个月大的淀粉样前体蛋白/早老素1（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)或运动组(Tg-Ex，Wt-Ex)承担12周，中等强度跑步机运行程序。因此,测试了所有小鼠的记忆功能和淀粉样β（Aβ）水平，并检查了皮质和海马组织中tau和蛋白激酶B（Akt）/糖原合酶激酶3（GSK3）的磷酸化。
结果：Tg-Sed小鼠记忆严重受损，Aβ水平较高，tau的磷酸化增加，GSK3α酪氨酸279和GSK3β酪氨酸216，但在两种组织中GSK3αserine21，GSK3βserine9和Aktserine473的磷酸化均低于各自组织中的Wt-Sed小鼠。Tg-Ex小鼠表现出记忆功能的显着改善以及较低水平的Aβ和较少的tau磷酸化（两种组织），GSK3α酪氨酸279（两种组织），和GSK3β酪氨酸216（仅海马），但是GSK3αserine21（两种组织）的磷酸化增加，GSK3βserine9（仅海马），和Aktserine473(两种组织)与相应组织中的Tg-Sed小鼠相比。
结论：中等强度有氧运动对改善9月龄APP/PS1小鼠的记忆功能非常有效，最有可能是通过皮质和海马中GSK3α/β磷酸化的差异调节。
方法：将六个月大的淀粉样前体蛋白/早老素1（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)或运动组(Tg-Ex，Wt-Ex)承担12周，中等强度跑步机运行程序。因此,测试了所有小鼠的记忆功能和淀粉样β（Aβ）水平，并检查了皮质和海马组织中tau和蛋白激酶B（Akt）/糖原合酶激酶3（GSK3）的磷酸化。
结果：Tg-Sed小鼠记忆严重受损，Aβ水平较高，tau的磷酸化增加，GSK3α酪氨酸279和GSK3β酪氨酸216，但在两种组织中GSK3αserine21，GSK3βserine9和Aktserine473的磷酸化均低于各自组织中的Wt-Sed小鼠。Tg-Ex小鼠表现出记忆功能的显着改善以及较低水平的Aβ和较少的tau磷酸化（两种组织），GSK3α酪氨酸279（两种组织），和GSK3β酪氨酸216（仅海马），但是GSK3αserine21（两种组织）的磷酸化增加，GSK3βserine9（仅海马），和Aktserine473(两种组织)与相应组织中的Tg-Sed小鼠相比。
结论：中等强度有氧运动对改善9月龄APP/PS1小鼠的记忆功能非常有效，最有可能是通过皮质和海马中GSK3α/β磷酸化的差异调节。
