Cognitive, Behavioral, and Systems NeuroscienceResearch PaperPharmacological investigations on potential of peroxisome proliferator-activated receptor-gamma agonists in hyperhomocysteinemia-induced vascular dementia in rats

The present study has been designed to investigate the potential of peroxisome proliferator-activated receptor-gamma ([PPAR]-γ) agonists, pioglitazone, and rosiglitazone in hyperhomocysteinemia-induced vascular dementia of rats. l-methionine was administered for 8 weeks to induce hyperhomocysteinemia and associated vascular dementia. Pioglitazone and rosiglitazone were administered to l-methionine-treated rats for 4 weeks (starting from 5th to 8th weeks of methionine treatment). Donepezil served as a positive control in this study. On 52nd day onward, the animals were exposed to Morris water maze (MWM) for testing learning and memory abilities. Vascular endothelial function, serum nitrite/nitrate levels, brain thiobarbituric acid reactive species (TBARS), brain reduced glutathione (GSH) levels, and brain acetylcholinesterase (AChE) activity were also measured. l-methionine-treated animals have shown impairment of learning, memory, endothelial function, decrease in serum nitrite/nitrate levels, and brain GSH levels along with increase in brain TBARS levels and AChE activity. Pioglitazone, rosiglitazone, and donepezil significantly improved hyperhomocysteinemia-induced impairment of learning, memory, endothelial dysfunction, and changes in various biochemical parameters. It is concluded that pioglitazone and rosiglitazone may be considered as potential pharmacological agents for the management of hyperhomocysteinemia-induced vascular dementia.

▶Study highlights the effect of PPAR-gamma agonists in l-methionine-induced vascular dementia. ▶Chronic l-methionine treatment produces significant degree of vascular dementia in mice. ▶Pioglitazone and rosiglitazone significantly reversed l-methionine-induced vascular dementia.