Treadmill exercise decreases incidence of Alzheimer’s disease by suppressing glycogen synthase kinase-3β expression in streptozotocin-induced diabetic rats

Abstract

Diabetes is a metabolic disorder, and it is considered as a major risk factor for Alzheimer’s disease (AD). In the present study, we evaluated whether treadmill exercise ameliorates progression of AD in relation with glycogen synthase kinase-3β (GSK-3β) activity using streptozotocin (STZ)-induced diabetic rats. For this study, step-down avoidance task, immunohistochemistry for glycogen synthase kinase-3β (GSK-3β) and tau, and western blot for phosphor-phosphoinositide 3 kinase (p-PI3K)/PI3K and phosphor-Akt (p-Akt)/Akt were performed. Diabetes mellitus was induced by intraperitoneal injection of STZ. The rats in the exercise groups were made to run on the treadmill for 30 min per one day, five times a week, during 12 weeks. The present results showed that short-term and long-term latencies in the step-down avoidance task were decreased by induction of diabetes, and treadmill exercise inhibited these latencies in the diabetic rats. Induction of diabetes suppressed the ratio of p-PI3K to PI3K and the ratio of p-Akt to Akt, and treadmill exercise increased these ratios in the diabetic rats. The numbers of GSK-3β-positive and tau-positive cells in the hippocampal dentate gyrus was higher in the diabetes-induction group than that in the control group, and treadmill exercise inhibited these numbers in the diabetic rats. In the present study, treadmill exercise suppressed hyperphosphorylation of tau in the hippocampus by decreased GSK-3β activity through PI3K/Akt pathway activation in the diabetic rats. Based on the present results, treadmill exercise may helpful to prevent diabetes-associated AD occurrence.

Characterization of prefrontal cortex microstructure and antioxidant status in a rat model of neurodegeneration induced by aluminium chloride and multiple low-dose streptozotocin

“…3), but no deposits of Congophilic materials (amyloid plaques) were observed. Moreover, although findings from the studies of Kim et al (2015) showed the presence of neurofibrillary tangle in the hippocampus of rats with STZinduced DM-associated AD pathology, the degree of prefrontal tau hyperphosphorylation associated with our AD + DM model is unclear as staining for phosphorylated tau could not be done.…”

Mechanisms of Aerobic Exercise Upregulating the Expression of Hippocampal Synaptic Plasticity-Associated Proteins in Diabetic Rats

“…Kang and Cho [39] found that 6 weeks of treadmill exercise upregulates the level of p-InR, p-PI3K, and p-Akt in the brains of AD rats. Kim et al [40] found that 12 weeks of aerobic treadmill exercise also significantly increases the levels of p-PI3K and p-Akt in the hippocampus of diabetic rats. In addition, 6 weeks of exercise increases the number of p-mTOR-positive neurons and astrocytes in the striatum, hippocampus, and amygdala of normal rats compared with the static control group [41].…”

Treadmill exercise ameliorates Alzheimer disease-associated memory loss through the Wnt signaling pathway in the streptozotocin-induced diabetic rats

“…To induce diabetes, a single intraperitioneal injection of STZ (50 mg/kg, dissolved in 0.01-M citrate buffer at pH 4.5; Sigma Chemical Co.) was given to each animal, as the previously described method ( Kim et al, 2015 ). Blood glucose levels were determined 3 days after STZ injection using a blood glucose tester (Arkray, Kyoto, Japan).…”