Aerobic Exercise Regulates Apoptosis through the PI3K/Akt/GSK-3β Signaling Pathway to Improve Cognitive Impairment in Alzheimer’s Disease Mice

Abstract

Neuronal apoptosis is an important factor in the etiology of Alzheimer’s disease (AD). Aerobic exercise (AE) enhances learning and memory, improves cognitive impairment, increases telomere binding protein expression, and decreases apoptosis regulators, but it remains unclear whether it can improve cognitive impairment caused by neuronal apoptosis in AD. Therefore, this study investigated whether an 8-week running table exercise intervention could reduce apoptosis and improve cognitive function in the hippocampal neurons of AD model mice. After the exercise intervention, we evaluated the learning memory ability (positioning, navigation, and spatial search) of mice using a Morris water labyrinth, Nissl staining, immunohistochemistry, and protein application to detect hippocampal PI3K/Akt/GSK-3β signaling pathway protein and hippocampal neuronal cell apoptosis protein B cell lymphoma 2 (Bcl-2) and apoptosis-promoting protein bcl-2-related X (Bax) protein expression. The results showed that aerobic exercise improved the location and spatial exploration ability of mice, increased the number of PI3K- and p-Akt-positive cells, increased the expression of PI3K, p-Akt, and bcl-2 proteins, decreased the expression of GSK-3β and Bax proteins, and increased the bcl-2/Bax ratio of mice. The results suggest that aerobic exercise can reduce apoptosis and improve cognitive function in AD mice. The molecular mechanism may involve activation of the PI3K/Akt/GSK-3β signaling pathway.

Aerobic exercise combined with chlorogenic acid exerts neuroprotective effects and reverses cognitive decline in Alzheimer’s disease model mice (APP/PS1) via the SIRT1/ /PGC-1α/PPARγ signaling pathway

“…The study found that escape latency and total distance traveled decreased during the experiment for both groups, with the wild control mice taking the shortest time and traveling the shortest distance and the AD mice taking a higher time than the wild control mice. The quadrant dwell time and number of crossings were better in the wild control group than in the experimental group, which is consistent with previous studies ( Wang X. et al, 2018 ; Ishida et al, 2020 ; Ryu et al, 2020 ; Web of Science, 2021 ; Lu et al, 2022 ; Peng et al, 2022 ), and we found that after EX/GCA/EX+GCA treatment, both memory and cognitive abilities were effectively alleviated in the mice, which is thought to be because the 8-week treatment delayed the progression of AD and effectively inhibited cognitive decline.…”

Unlocking the Therapeutic Potential of Irisin: Harnessing Its Function in Degenerative Disorders and Tissue Regeneration

“…The Phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is another common mechanism that is predominantly regulated by mechanical stimuli in various tissues frequently seen in muscle [ 61 , 62 ] and brain [ 63 , 64 ]. Mechanical stress activates β1 Integrin, which in turn triggers integrin-linked kinases (ILK) [ 65 ] and focal adhesion kinase (FAK) [ 46 , 66 ], leading to the activation of the PI3K/Akt/mammalian target of rapamycin complex 1 (mTORC1) process.…”

“…It has been proposed that resistance exercise promotes muscle hypertrophy by increasing systemic growth factors such as IGF-1, which activate the PI3K/Akt/mTORC1 signaling axis to enhance muscle protein synthesis [ 46 , 67 ]. The exercise-induced growth factor BDNF also plays a crucial role in neuronal survival [ 68 ], promoting regeneration in injured brains [ 69 ] and resistance to degenerative disorders such as Alzheimer’s disease [ 63 ] via the PI3K/Akt signaling axis [ 68 , 70 , 71 , 72 ].…”

Precious but convenient means of prevention and treatment: physiological molecular mechanisms of interaction between exercise and motor factors and Alzheimer’s disease

“…In normal brain, Bcl-2 is highly expressed and saves cells from apoptosis, while in AD brain, Bcl-2 expression is suppressed, Bax is overexpressed, and Bcl-2/Bax homeostasis is disrupted, triggering neuronal apoptosis. In the latest study, it was found that aerobic exercise improved neuronal apoptosis and was accompanied by activation of PI3K/AKT Further study revealed that it was the activation of PI3K/AKT that reversed the decrease of Bcl-2 expression and inhibited Bax expression, allowing the balance to be restored ( Peng et al, 2022 ). Figure 4 .…”