TY - JOUR
T1 - Telmisartan protects against cognitive decline via up-regulation of brain-derived neurotrophic factor/tropomyosin-related kinase B in hippocampus of hypertensive rats
AU - Kishi, Takuya
AU - Hirooka, Yoshitaka
AU - Sunagawa, Kenji
N1 - Funding Information:
This study was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science ( 22790709 ) and, in part, a Kimura Memorial Foundation Research Grant .
PY - 2012/12
Y1 - 2012/12
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jjcc.2012.08.004
DO - 10.1016/j.jjcc.2012.08.004
M3 - Article
C2 - 22948091
AN - SCOPUS:84869086473
SN - 0914-5087
VL - 60
SP - 489
EP - 494
JO - Journal of Cardiology
JF - Journal of Cardiology
IS - 6
ER -