Effects of Treadmill Exercise on Hippocampal Inflammation and Behavioural Changes in Type 2 Diabetic Rats
Objective:To investigate the effects and possible mechanisms of 8 weeks of treadmill exercise on the hippocampal toll-like receptor 4/myeloid differentiation factor 88(TLR4/MyD88)signalling pathway and behavioural disorders in type 2 diabetic Goto-Kakizaki(GK)rats.Methods:Male GK rats were randomly divided into 2 groups:Diabetes group,Diabetes+Exe group and 8 rats in each group.In addition,male Wistar rats were randomly divided into 2 groups:Con group,Con+Exe group and 8 rats in each group.The rats of Con+Exe group and Diabetes+Exe group were treated with treadmill exercise(60 min daily and 5 days per week for 8 weeks).Results:(1)Compared with the Con group,the FBG level of rats in the Diabetes group increased significantly(P<0.01)and the FINS level decreased significantly(P<0.01);Compared with the Diabetes group,the FBG level of rats in the Diabetes+Exe group decreased significantly(P<0.05)and the FINS level increased significantly(P<0.05).(2)Compared with the Con group,type 2 diabetic GK rats(Diabetes group)with more tension showed less spontaneous activity and exploratory behaviour.For example,they were more likely to be close to the edge of open field activity,to have abnormal faecal metabolism and to spend more time immobile(P<0.05 or P<0.01),while treadmill exercise had some improvement in behavioural disturbances(P<0.05 or P<0.01).(3)The results of HE staining in the hippocampus showed that the volume of the hippocampus in the Diabetes group decreased,and the pyramidal cells in hippocampal CA1 were disordered,swollen,and the cell gap widened.The hippocampal volume of rats in the Diabetes+Exe group was basically normal,and the pyramidal cells in the hippocampal CA1 area were slightly ordered.(4)The protein expression levels of TLR4,MyD88,TRAF6,ICAM1,NFκB p65,p-IκBα,TNF-αand IL-6 in the hippocampus of rats in the Diabetes group were significantly increased compared to the Con group(P<0.05 or P<0.01).The protein expression levels of TLR4,MyD88,TRAF6,NFκB p65,p-IκBα,TNF-αand IL-6 in the hippocampus of rats in the Diabetes+Exe group were significantly decreased(P<0.05 or P<0.01)compared with Diabetes group.The above results suggest that exercise intervention can effectively improve the behavioural disorders in type 2 diabetic GK rats,and the mechanism may be related to its pro-inflammatory effect of inhibiting the hippocampal TLR4/MyD88 signalling pathway.
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