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

Autor: Solmaz V; Department of Neurology, Turhal State Hospital, Tokat, Turkey. Electronic address: solmaz.volkan@yahoo.com., Çınar BP; Department of Neurology, Giresun State Hospital, Giresun, Turkey., Yiğittürk G; Department of Histology & Embryology, Ege University School of Medicine, İzmir, Turkey., Çavuşoğlu T; Department of Histology & Embryology, Ege University School of Medicine, İzmir, Turkey., Taşkıran D; Department of Physiology, Ege University School of Medicine, İzmir, Turkey., Erbaş O; Department of Physiology, Istanbul Bilim University School of Medicine, İstanbul, Turkey.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2015 Oct 15; Vol. 765, pp. 482-7. Date of Electronic Publication: 2015 Sep 16.
DOI: 10.1016/j.ejphar.2015.09.024
Abstrakt: Recent studies suggest a possible link between type 2 diabetes and Alzheimer's disease (AD). Glucogan-like 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 µgr/kg/day through intraperitoneally for two weeks. Then, cognitive performance (passive avoidance learning), brain tumor necrosis factor alpha (TNF-α) levels, choline acetyltransferase (ChAT) activity and hippocampal neuronal count were determined. While the brain TNF-α levels were significantly high in the saline-treated STZ group, exenatide treatment suppressed the increase in TNF-α 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.
(Copyright © 2015 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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