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

Abstract

We investigated the effects of aerobic exercise on the expression of hippocampal synaptic plasticity-associated proteins in rats with type 2 diabetes and their possible mechanisms. A type 2 diabetes rat model was established with 8 weeks of high-fat diet combined with a single intraperitoneal injection of streptozotocin (STZ). Then, a 4-week aerobic exercise intervention was conducted. Memory performance was measured with Y maze tests. The expression and activity of synaptic plasticity-associated proteins and of proteins involved in the PI3K/Akt/mTOR, AMPK/Sirt1, and NFκB/NLRP3/IL-1β signaling pathways were evaluated by western blot. Our results show that aerobic exercise promotes the expression of synaptic plasticity-associated proteins in the hippocampus of diabetic rats. Aerobic exercise also activates the PI3K/Akt/mTOR and AMPK/Sirt1 signaling pathways and inhibits the NFκB/NLRP3/IL-1β signaling pathway in the hippocampus of diabetic rats. Therefore, modulating the PI3K/Akt/mTOR, AMPK/Sirt1, and NFκB/NLRP3/IL-1β signaling pathways is probably the mechanism of aerobic exercise upregulating the expression of hippocampal synaptic plasticity-associated proteins in diabetic rats.

Stanniocalcin-1 Overexpression Prevents Depression-Like Behaviors Through Inhibition of the ROS/NF-κB Signaling Pathway

“…For instance, resveratrol-activated ROS/NF-κB signaling pathway aggravated phosphine-induced hepatic injury partially by reducing SOD and CAT, increasing the levels of TNF-α, IL-1β, and IL-6, and promoting apoptosis of hepatocytes ( 28 ). The aerobic exercise-induced downregulation of the NF-κB/NLRP3/IL-1β signaling pathway could increase the expression of proteins related to hippocampal synaptic plasticity in diabetic rats ( 29 ). Moreover, inhibition of NF-κB by hesperidin could aid in diminishing neuronal degeneration and hippocampal inflammation, while improving learning as well as cognitive responses in a sevoflurane anesthetized neonatal rat model ( 30 ).…”

Research Progress of Mitochondrial Mechanism in NLRP3 Inflammasome Activation and Exercise Regulation of NLRP3 Inflammasome

“…As shown in Table 1 , endurance training was most widely used and treadmill running was the main exercise mode, followed by swimming and voluntary wheel running. It is worth mentioning that moderate-intensity treadmill exercise over 4 weeks was generally demonstrated to significantly inhibit the overactivation of the NLRP3 inflammasome of mice and rats in adipose tissue [ 49 , 50 ], liver [ 51 , 52 ], myocardium [ 53 , 54 , 55 ] hippocampus [ 56 , 57 , 58 , 59 , 60 , 61 ], prefrontal cortex [ 63 ] and substantia nigra [ 62 ] which were caused by metabolic disorder, DEN (diethylnitrosamine) damage, hypoxia, myocardial hypertrophy, aging, myocardial infarction, ovariectomy, Alzheimer’s’ disease, depression, cerebral ischemia and ischemia reperfusion. Similarly, human studies also showed that chronic moderate-intensity running significantly reduced the NLRP3 inflammasome activation in peripheral blood mononuclear cells (PBMCs) of healthy young men, while chronic high-intensity running activated the NLRP3 inflammasome [ 64 ].…”

Impact of exercise on hippocampal neurogenesis in hyperglycemic diabetes

“…Exercise protects central nervous system injury and improves learning ability and memory function (Lee et al, 2018;Sim, 2014). Aerobic exercise promotes the expression of synaptic plasticity-associated proteins in the hippocampus of diabetic rats (Li et al, 2019).…”

“…Physical exercise increases the number of neuronal and non-neuronal cortical cells and hippocampal neuronal cells in adolescent rats (Victorino et al, 2017). Neurogenesis can be an important contributor to improving learning and memory through exercise (Baek, 2016;Li et al, 2019).…”