Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala-147002, Punjab, India.
Pharmacol Biochem Behav. 2011 Dec;100(2):320-9. doi: 10.1016/j.pbb.2011.08.020. Epub 2011 Aug 27.
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-γ) 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-γ 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-γ modulators pioglitazone and rosiglitazone may be considered as potential pharmacological agents for the management of diabetes induced VaD.
血管性痴呆（VaD）是第二常见的痴呆症。我们最近报道糖尿病可导致大鼠 VaD。本研究旨在研究过氧化物酶体增殖物激活受体-γ（PPAR-γ）激动剂在 Wistar 白化大鼠糖尿病诱导的 VaD 中的潜在作用。大鼠单次给予链脲佐菌素（STZ）以诱导糖尿病。采用 Morris 水迷宫（MWM）试验测试学习和记忆能力。还测试了血清葡萄糖、体重、血管内皮功能、血清亚硝酸盐/硝酸盐水平、主动脉和大脑氧化应激水平（即主动脉超氧阴离子水平、大脑硫代巴比妥酸反应性物质和大脑谷胱甘肽水平）以及大脑乙酰胆碱酯酶活性。STZ 处理的动物在 MWM 上表现不佳，因此反映出学习和记忆行为受损，体重显著减轻，血管内皮功能受损，血清亚硝酸盐/硝酸盐水平降低，血清葡萄糖、主动脉和大脑氧化应激水平以及大脑乙酰胆碱酯酶活性升高。PPAR-γ 激动剂吡格列酮和罗格列酮的治疗显著逆转了糖尿病诱导的学习和记忆行为、内皮功能以及各种生化参数的变化。结论是，PPAR-γ 调节剂吡格列酮和罗格列酮可被认为是治疗糖尿病诱导的 VaD 的潜在药物。
