Abstract
Purpose: This study was designed to demonstrate potential
neuroprotective and autophagic activity of exenatide in rodent AD model.
Experimental Approach: Thirty adult Sprague-Dawley male rats were
divided into 3 groups (10 rats each); Group 1; control normal group,
Group 2; AD pathological group, Group 3; exenatide treated group. All
drugs were given intraperitoneal (IP) for 42 days. Behavioral changes
using Morris water maze test has been evaluated, gene expressions of
beclin-1 and the mammalian target of rapamycin (mTOR) in the hippocampus
were assessed. Examination of hippocampal tissue using hematoxylin &
eosin (H&E) stain and ultrastructural analyses were also done. Data
were analyzed by using the statistical package for the social sciences
(SPSS). Key Results: Exenatide alleviated both behavioral and
pathological changes compared to pathological group. Exenatide treated
group was found to improve autophagic activity by increasing beclin-1
and decreasing mTOR gene expression. Exenatide treatment significantly
prevented hippocampal neuronal degeneration demonstrated by H&E.
Moreover, accumulation of autophagic vacuoles in ultrastructure study of
hippocampus, alleviated in exenatide group compared to pathological
group indicating enhanced autophagic activity by exenatide. Conclusion
and Implications: The results of the present study clearly indicated
exenatide might have beneficial effects on impaired cognitive
performance and hippocampal neuronal viability in AD by increasing
autophagic activity. Increased beclin-1 seems to be the initiating
player in this disease modifying effect and this supports the assumption
of a disease modifying activity of exenatide through the autophagic
activity.