Moderate-Intensity Treadmill Exercise Regulates GSK3α/β Activity in the Cortex and Hippocampus of APP/PS1 Transgenic Mice

Jul 31, 2024Journal of integrative neuroscience

Moderate treadmill exercise changes key enzyme activity in thinking and memory areas of Alzheimer’s model mice

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Abstract

Twelve weeks of moderate-intensity exercise improved memory function in Tg mice compared to sedentary Tg mice.

Tg-Sed mice displayed severely impaired memory and higher levels of amyloid β (Aβ) compared to Wt-Sed mice.
In Tg-Sed mice, increased phosphorylation of tau and GSK3 proteins was observed relative to Wt-Sed mice.
Tg-Ex mice exhibited significant memory improvement alongside lower Aβ levels and reduced tau phosphorylation compared to Tg-Sed mice.
Exercise in Tg-Ex mice was associated with increased phosphorylation of certain GSK3 and Akt proteins in both brain regions.

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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.

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Moderate-Intensity Treadmill Exercise Regulates GSK3α/β Activity in the Cortex and Hippocampus of APP/PS1 Transgenic Mice

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