Angiotensin II type 1 receptor blockade diminishes negative effect of chronic stress on memory via upregulation of brain-derived neurotrophic factor

Abstract

IntroductionA critical need exists for progress in the characterization of targets for pro-cognitive drug discovery. We previously demonstrated that Telmisartan (TLM), an angiotensin type 1 receptor (AT1) blocker and partial agonist of peroxisome proliferator-activated receptor gamma (PPARγ), alleviates cognitive decline in chronically stressed rats. Understanding of mechanistic background of this phenomenon is hampered by both dual binding sites of TLM and limited data on the molecular consequences of central AT1 blockade and PPARγ activation.ObjectivesTo discriminate molecular effects of AT1 blockade and PPARγ activation in stress induced memory impairment.AimsIn this study, we investigated mechanism of neuroprotection provided by TLM in chronic psychological stress.MethodsWe analyzed BDNF gene expression in the hippocampus (HIP) and medial prefrontal cortex (mPFC) in chronically restrained stressed Wistar rats (2.5 h, 21 days), repeatedly treated with TLM (1 mg/kg), GW9662 (0.5 mg/kg) – a selective PPARγ receptor antagonist, or both in combination. TATA box binding protein (Tbp) was an internal control for expression studies.ResultsAlterations of mRNA expression of BDNF are shown on Figs. 1 and 2.ConclusionsAT1 receptor blockade restores cognitive functions in chronically stressed subjects, which is associated with changes in primarily cortical gene expression.Disclosure of interestThe authors have not supplied their declaration of competing interest.