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

Jingjing Li,Beibei Liu,Jingyun Hu,Mingming Li,Yuran Liu,Shujie Lou,Qian Wang,Feng Li

doi:10.1155/2019/7920540

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.

Highlights

Our previous metabolomics study found impaired glucose metabolism in the hippocampus of diabetic rats, mainly indicated by inhibition of the TCA cycle and activation of the glycolysis pathway, polyol pathway, and pentose phosphate pathway [1]
We investigated whether aerobic exercise can inhibit inflammation in the hippocampus of diabetic rats by analyzing the concentrations and activities of proteins involved in the AMPK/Sirt1 and NFκB/NLRP3/IL-1β signaling pathways
The levels of Ac-NFκB, NFκB, NLRP3, and IL-1β were higher in DM rats than in C rats and were lower in TDM rats than in DM rats (Figure 5). These results indicate that diabetes inhibits the AMPK/Sirt1 pathway and activates the NFκB/NLRP3/IL-1β pathway and that aerobic exercise promotes the AMPK/Sirt1 pathway and inhibits inflammation induced by diabetes in the hippocampus

Summary

Introduction

Our previous metabolomics study found impaired glucose metabolism in the hippocampus of diabetic rats, mainly indicated by inhibition of the TCA (tricarboxylic acid) cycle and activation of the glycolysis pathway, polyol pathway, and pentose phosphate pathway [1]. As SYN (synaptophysin), Homer, and NMDAR (N-methyl-D-aspartic acid receptor) are all important presynaptic (SYN) or postsynaptic (Homer and NMDAR) proteins involved in Neural Plasticity synaptic plasticity and closely related to cognition, it has been reported that hippocampal SYN and NMDAR1 expressions were downregulated in diabetic rats or AD (Alzheimer’s disease) mice [5,6,7,8]. It remains unclear whether the alterations of hippocampal glucose metabolism in type 2 diabetes affect the insulin signaling pathway and how this would affect the expression of synaptic plasticity-associated proteins

Methods

Results

Conclusion