Strength exercise suppresses STZ‐induced spatial memory impairment and modulates BDNF/ERK‐CAMKII/CREB signalling pathway in the hippocampus of mice

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has generated scientific interest because of its prevalence in the population. Studies indicate that physical exercise promotes neuroplasticity and improves cognitive function in animal models and in human beings. The aim of the present study was to investigate the effects of strength exercise on the hippocampal protein contents and memory performance in mice subjected to a model of sporadic AD induced by streptozotocin (STZ). Swiss mice received two injections of STZ (3 mg/kg, intracerebroventricular). After 21 days, they began physical training using a ladde. Mice performed this protocol for 4 weeks. After the last exercise training session, mice performed the Morris Water Maze test. The samples of hippocampus were excised and used to determine protein contents of brain-derived neurotrophic factor (BDNF), extracellular signal-regulated kinase-Ca 2+ (ERK), calmodulindependent protein kinase (CAMKII) and cAMP-response element-binding protein (CREB) signalling pathway. Strength exercise was effective against the decrease in the time spent and distance travelled in the target quadrant by STZ-injected mice. Strength exercise was also effective against the reduction of mature BDNF, tropomyosin receptor kinase B and neuronal nuclear antigen (NeuN) hippocampal protein levels in STZ mice. The decrease in the hippocampal ratio of pERK/ERK, pCAMKII/CAMKII and pCREB/CREB induced by STZ was reversed by strength exercise. Strength exercise decreased Bax/Bcl2 ratio in the hippocampus of STZ-injected mice. The present study demonstrates that strength exercise modulated the hippocampal BDNF/ERK-CAMKII/CREB signalling pathway and suppressed STZ-induced spatial memory impairment in mice.

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

“…In a previous study, exercise increased Bcl-2 and decreased Bax levels and inhibited apoptosis in the mouse hippocampus, possibly through activation of the PI3K/Akt/GSK-3 β pathway. A study of AD mice subjected to 4 weeks of strength training found that exercise decreased the Bax/Bcl-2 ratio in the hippocampus of mice [ 48 ]. A study on 6 weeks of aerobic exercise in AD rats found that exercise increased Bcl-2, decreased Bax content, increased the Bcl-2/Bax ratio, and inhibited apoptosis in AD [ 49 ].…”

Aerobic exercise attenuates LPS-induced cognitive dysfunction by reducing oxidative stress, glial activation, and neuroinflammation

“…Tong et al [ 61 ] reported that wheel running exercise for 3 weeks reduced the expression of mRNAs of apoptosis-associated genes, such as the Bcl-2 gene family, and neuronal death. Likewise, both 4 weeks and 6 weeks of exercise training increased the expression of Bcl-2, decreased the expression of Bax, and inhibited apoptosis in both AD mice and rats [ 62 , 63 ]. In this study, we confirmed that 4-week aerobic exercise can enhance learning memory and attenuate hippocampal and cortical neuronal apoptosis in AD mice by increasing the expression of Bcl-2 and reducing that of Bax, caspase 3, and PARP-1.…”

Recent advances on the molecular mechanisms of exercise-induced improvements of cognitive dysfunction

“…In addition, several studies have revealed other factors or mechanisms. For example, Martini et al suggested that power exercise inhibits streptozotocin-induced spatial memory deficits in AD mice by activating the phosphorylation of the hippocampal BDNF/ERK/CaMKII/CREB signaling pathway [ 84 ]. Moreover, researchers have proposed that the mechanism by which exercise increases BDNF levels in brain tissue may be due to the release of an endogenous histone deacetylase (HDAC) inhibitor.…”