mTOR and tau phosphorylated proteins in the hippocampal tissue of rats with type 2 diabetes and Alzheimer's disease.

Abstract

This study explored the effects of mammalian target of rapamycin (mTOR) on the increased risk of developing Alzheimer's disease (AD) in rats with type 2 diabetes mellitus (T2DM). Male Sprague-Dawley rats were randomly divided into four groups: control, T2DM, AD and T2DM+AD. Changes in the learning and memory abilities of the rats were observed using the Morris water maze. mTOR activity and tau protein hyperphosphorylation in the hippocampus were analyzed by immunohistochemical staining and RT-PCR. The learning and memory abilities of the experimental rats were weakened compared with those of the control group. The T2DM+AD group revealed significant changes over the T2DM and AD groups. Compared with the control, T2DM and AD groups, the mTOR protein and mRNA levels, hyperphosphorylation of tau protein and total tau protein mRNA levels were significantly increased in the T2DM+AD group. T2DM may excessively activate mTOR in the hippocampal tissue by impairing insulin signaling, thereby increasing the extent of tau hyperphosphorylation and promoting the occurrence of AD.