ABSTRACT
Objective To investigate the effects and possible mechanisms of different modes of mild treadmill exercise on cognitive function in Alzheimer's disease(AD) APP transgenic mice.Methods Twenty-four 6-month-old APP+ mice were randomly and equally divided into the four groups:control group(Con),regular exercise group(RE),irregular time-of-day exercise group (ITE) and irregular different duration exercise group(IDDE).After treadmill exercise,the spatial cognitive ability was tested.Soluble and insoluble Aβ40,42 levels,activity of β-secretase and γ-secretase in hippocampal tissue were compared among 4 groups.The mRNA levels of NEP,IDE and MMP-9 in the hippocampal tissue were detected.The number of hippocampal survival neurons and protein levels of BDNF,TrkB and p-TrkB were detected.Results Compared with the control group,the spatial cognitive ability in the RE group was significantly increased(P＜0.05),the levels of soluble and insoluble Aβ40,42 and activity of β-secretase and γ-secreatase were significantly reduced in the hippocampal tissue of th RE group(P＜ 0.05).However,the mRNA levels of NEP,IDE and MMP-9 had no statistically significant difference among the four groups(P＞0.05).Compared with the control group,the number of survival neurons and protein levels of BDNF and p-TrkB in the hippocampal of the RE group tissue were significantly increased(P＜0.05).The cognitive function,levels of Aβ40,42,BDNF and p-TrkB,number of survival neurons in the RE group had statistically significant differences when compared with the ITE and IDDE groups(P＜0.05).Conclusion Mild and regular treadmill exercise can effectively increase the cognitive function of AD mice,which might be related with the regulation of BDNF/TrkB pathway.