Telmisartan protects against cognitive decline via up-regulation of brain-derived neurotrophic factor/tropomyosin-related kinase B in hippocampus of hypertensive rats

Takuya Kishi, Yoshitaka Hirooka, Kenji Sunagawa

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Background and purpose: Cognitive decline may occur as a result of hypertension, and is dependent on the function of hippocampus. Brain-derived neurotrophic factor (BDNF) mediated by angiotensin II-induced oxidative stress protects against cell death in hippocampus. Angiotensin II receptor blocker (ARB), candesartan, activates BDNF in the hippocampus. Furthermore, peroxisome proliferator-activated receptor (PPAR)-gamma activation in the brain prevents brain damage. Telmisartan, a unique ARB with PPAR-gamma stimulating activity, protects against cognitive decline partly because of PPAR-gamma activation. The aim of the present study was to determine whether telmisartan protects against cognitive decline via up-regulation of BDNF and its receptor tropomyosin-related kinase B (TrkB) in the hippocampus of hypertensive rats, partly because of PPAR-gamma activation. Methods and results: We divided stroke-prone spontaneously hypertensive rats (SHRSPs), as hypertensive and vascular dementia model rats, into five groups, telmisartan-treated (TLM), TLM. +. GW9662, a PPAR-gamma inhibitor, -treated (T. +. G), GW9662-treated (GW), TLM. +. ANA-12, a TrkB antagonist, -treated (T. +. A), and vehicle-treated SHRSPs (VEH). After the treatment for 28. days, systolic blood pressure did not change in all groups. However, BDNF expression in the hippocampus was significantly higher in TLM than in VEH to a greater extent than in T. +. G. Cognitive performance was significantly higher in TLM than in VEH to a greater extent than in T. +. G, and was not different between T. +. A, GW, and VEH. Conclusion: Telmisartan protects against cognitive decline via up-regulation of BDNF/TrkB in the hippocampus of SHRSPs, partly because of PPAR-gamma activation independent of blood pressure-lowering effect.

Original languageEnglish
Pages (from-to)489-494
Number of pages6
JournalJournal of Cardiology
Volume60
Issue number6
DOIs
Publication statusPublished - Dec 1 2012

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Brain-Derived Neurotrophic Factor
PPAR gamma
Hippocampus
Up-Regulation
Angiotensin Receptor Antagonists
Blood Pressure
trkB Receptor
Vascular Dementia
tropomyosin kinase
telmisartan
Cognitive Dysfunction
Brain
Inbred SHR Rats
Angiotensin II
Oxidative Stress
Cell Death
Stroke
Hypertension

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Telmisartan protects against cognitive decline via up-regulation of brain-derived neurotrophic factor/tropomyosin-related kinase B in hippocampus of hypertensive rats. / Kishi, Takuya; Hirooka, Yoshitaka; Sunagawa, Kenji.

In: Journal of Cardiology, Vol. 60, No. 6, 01.12.2012, p. 489-494.

Research output: Contribution to journalArticle

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