Rosiglitazone rescues memory impairment in Alzheimer’rats：mechanisms involving regulation of insulin-degrading enzyme and glycogen synthase kinese-3β

Abstract:

Objective：To investigate the effects of peroxisome proliferator-activated receptor γ（PPARγ） agonist-rosiglitazone（RTZ） on the cognition，amyloid β-peptide（Aβ） and Tau in the Alzheimer’s disease（AD） rats and to explore its potential mechanisms of at－tenuating learning and memory deficits. Methods：Dementia model was established by treating rats with intracerebroventricular strepto－zotocin injection. RTZ was administered to rats in dementia model. On the 21st d from the 1st STZ injection，spatial learning and memory of rats were tested in Morris water maze. Expressions of insulin-degrading enzyme（IDE），glycogen synthase kinase-3β（GSK-3β），phospho-GSK-3β（pGSK-3β），Tau and phospho-Tau（pTau） were measured by Western blot. Aβ40 and Aβ42 levels in the brain of AD rats were tested by immunohistochemistry. Results：AD rats administrating RTZ exhibited better spatial learning and memory abilities（P<0.001） and had lower Aβ levels than untreated AD rats. Western blot demonstrated that RTZ decreased IDE ex－pression（P=0.028），GSK-3β activity（P=0.012） and pTau level（P=0.001）. Immunohistochemical results demonstrated that RTZ re－duced Aβ40 and Aβ42 levels in the cerebral cortex. Conclusions：RTZ-mediated cognitive improvement of AD rats does corre－late with the expression of IDE and GSK-3β.