Quinazoline Alkylthio Derivative Reduces Autophagy and Improves Memory in Rat Model of Dementia Through mTOR Signaling Pathway Regulation

Abstract

The present study evaluated quinazoline alkylthio derivative (QATD) for possible role in the
treatment of vascular dementia (VD) in rat model. The established T‑maze test was used for assessment
of behavioural changes and Morris water maze (MWM) test for analysis of spatial learning in rats. Light
microscopy using Nissl‑staining was used to determine the survival of neurons in rat hippocampus and
expression of proteins was measured by western blotting. The study demonstrated that QATD treatment
of the VD rats significantly (p < 0.05) alleviated the impairment in spontaneously altered behaviours and
significantly (p < 0.05) reduced escape latency. VD mediated decrease in distance travelled, swim time and
count of platform crossings was significantly (p < 0.02) alleviated by QATD treatment of the rats. Moreover,
in QATD treated rats, VD mediated increase in Beclin-1 and Microtubule-associated protein light chain 3II
(LC3II) expression in the hippocampus tissues was significantly (p < 0.05) alleviated. In addition, QATD
treatment prevented suppression of mammalian target of rapamycin (mTOR) phosphorylation in VD rat
hippocampus tissues. However, rapamycin mediated suppression of p-mTOR and elevation of Beclin 1 and
LC3II expression in rat hippocampus could not be alleviated by QATD treatment. In summary, QATD effec‑
tively prevents VD mediated cognitive impairment and neuronal damage in the rats. Moreover, autophagy
was inhibited and the mTOR pathway activated in rats with VD by QATD treatment. Therefore, QATD may
be studied further as a therapeutic agent for treatment of dementia.