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

Published online by Cambridge University Press:  23 March 2020

D. Wincewicz  and
A. Juchniewicz
D. Wincewicz*
Affiliation:
Medical University of Bialystok, Department of Clinical Pharmacology, Bialystok, Poland
A. Juchniewicz
Affiliation:
Medical University of Bialystok, Department of Clinical Molecular Biology, Bialystok, Poland
*
*Corresponding author.

Abstract

Introduction

A 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.

Objectives

To discriminate molecular effects of AT1 blockade and PPARγ activation in stress induced memory impairment.

Aims

In this study, we investigated mechanism of neuroprotection provided by TLM in chronic psychological stress.

Methods

We 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.

Results

Alterations of mRNA expression of BDNF are shown on Figs. 1 and 2.

Conclusions

AT1 receptor blockade restores cognitive functions in chronically stressed subjects, which is associated with changes in primarily cortical gene expression.

Disclosure of interest

The authors have not supplied their declaration of competing interest.

Type
FC58
Information
European Psychiatry , Volume 33 , Issue S1: Abstracts of the 24th European Congress of Psychiatry , March 2016 , pp. S94
Copyright
Copyright © European Psychiatric Association 2016

Fig. 1 Effect of chronic stress (2.5 h, 21 days), chronic TLM (1 mg/kg, 21 days), chronic GW9662 (0.5 mg/kg. 21 days) or all in combination on mRNA BDNF expression in the mPFC (BDNF/Tbp ratio). Bars represent mean ± SEM; n = 5; ** P < 0.01; Control vs. Stress; ### P < 0.001 Stress vs. Stress + TLM and Stress vs. Stress + TLM + GW9662.

Fig. 2 Effect of chronic stress (2.5 h, 21 days), chronic TLM (1 mg/kg, 21 days), chronic GW9662 (0.5 mg/kg, 21 days) or all in combination on mRNA BDNF expression in the HIP (EDNF/Tbp ratio). Bars represent means ± SEM; n = 5; *P < 0.05; Stress vs. Stress + TLM and Stress vs. Stress + TLIVH-GW9662.

Figure 0

Fig. 1 Effect of chronic stress (2.5 h, 21 days), chronic TLM (1 mg/kg, 21 days), chronic GW9662 (0.5 mg/kg. 21 days) or all in combination on mRNA BDNF expression in the mPFC (BDNF/Tbp ratio). Bars represent mean ± SEM; n = 5; ** P < 0.01; Control vs. Stress; ### P < 0.001 Stress vs. Stress + TLM and Stress vs. Stress + TLM + GW9662.

Figure 1

Fig. 2 Effect of chronic stress (2.5 h, 21 days), chronic TLM (1 mg/kg, 21 days), chronic GW9662 (0.5 mg/kg, 21 days) or all in combination on mRNA BDNF expression in the HIP (EDNF/Tbp ratio). Bars represent means ± SEM; n = 5; *P < 0.05; Stress vs. Stress + TLM and Stress vs. Stress + TLIVH-GW9662.

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