Exenatide reduces TNF-alpha expression and improves hippocampal neuron numbers and memory in streptozotocin treated rats

Abstract

Recent studies suggest a possible link between type 2 diabetes and Alzheimer's disease (AD). Glucoganlike peptide 1 (GLP-1) facilitates insulin release from pancreas under hyperglycemic conditions. In addition to its metabolic effects, GLP-1 and its long-lasting analogs, including exenatide can stimulate neurogenesis and improve cognition in rodent AD model. The aim of the present study was to investigate the effects of exenatide on hippocampal cellularity, cognitive performance and inflammation response in a rat model of AD. Fourteen rats were used to create AD model using intracerebroventricular (ICV) streptozotocin (STZ) infusion while 7 rats were administered 0.9% NaCl only (sham-operated group). Following stereotaxic surgery, STZ received rats were randomly distributed into two groups, and treated with either saline or exenatide 20 mu gr/kg/day through intraperitoneally for two weeks. Then, cognitive performance (passive avoidance learning), brain tumor necrosis factor alpha (TNF-alpha) levels, choline acetyltransferase (ChAT) activity and hippocampal neuronal count were determined. While the brain TNF-alpha levels were significantly high in the saline-treated STZ group, exenatide treatment suppressed the increase in TNF-alpha levels. Saline-treated STZ group showed reduced ChAT activity compared to sham group. However, exenatide significantly preserved brain ChAT activity. The cognitive performance was also impaired in saline group while exenatide improved memory in rats. Moreover, exenatide treatment significantly prevented the decrease in hippocampal neurons. Overall, the results of the present study clearly indicated exenatide might have beneficial effects on impaired cognitive performance and hippocampal neuronal viability in AD by suppressing the inflammation response and increasing cholinergic activity. (C) 2015 Elsevier B.V. All rights reserved.