Behavioral and biochemical investigations to explore pharmacological potential of PPAR-gamma agonists in vascular dementia of diabetic rats

Vascular dementia (VaD) is the second most common dementing illness. We have recently reported that diabetes induces VaD in rats. The present study has been designed to investigate the potential of peroxisome-proliferator-activated receptors-gamma (PPAR-gamma) agonists in diabetes induced VaD of Wistar Albino rats. The rats were administered, single dose of streptozotocin (STZ) for the induction of diabetes. Morris water-maze (MWM) test was employed for testing learning and memory. Serum glucose, bodyweight, vascular endothelial function, serum nitrite/nitrate levels, aortic and brain oxidative stress levels (viz. aortic superoxide anion levels, brain thiobarbituric acid reactive species and brain glutathione levels) and brain acetylcholinesterase activity were also tested. STZ treated animals performed poorly on MWM hence reflecting impairment of learning and memory behavior with a significant reduction in body weight, impairment of vascular endothelial function, and decrease in serum nitrite/nitrate levels, increase in serum glucose, aortic and brain oxidative stress levels and brain acetylcholinesterase activity. Treatment of PPAR-gamma agonists, pioglitazone as well as rosiglitazone significantly reversed, diabetes induced impairment of learning and memory behavior, endothelial function, and changes in various biochemical parameters. It is concluded that PPAR-gamma modulators pioglitazone and rosiglitazone may be considered as potential pharmacological agents for the management of diabetes induced VaD. (C) 2011 Elsevier Inc. All rights reserved.