Telmisartan prevented cognitive decline partly due to PPAR-gamma activation.
Telmisartan is a unique angiotensin receptor blocker (ARB) and partial agonist of peroxisome proliferator-activated receptor (PPAR)-gamma. Here, we investigated the preventive effect of telmisartan on cognitive decline in Alzheimer disease. In ddY mice, intracerebroventricular injection of Abeta 1-40 significantly attenuated their cognitive function evaluated by shuttle avoidance test. Pretreatment with a non-hypotensive dose of telmisartan significantly inhibited such cognitive decline. Interestingly, co-treatment with GW9662, a PPAR-gamma antagonist, partially inhibited this improvement of cognitive decline. Another ARB, losartan, which has less PPAR-gamma agonistic effect, also inhibited Abeta-injection-induced cognitive decline; however the effect was smaller than that of telmisartan and was not affected by GW9662. Immunohistochemical staining for Abeta showed the reduced Abeta deposition in telmisartan-treated mice. However, this reduction was not observed in mice co-administered GW9662. These findings suggest that ARB has a preventive effect on cognitive impairment in Alzheimer disease, and telmisartan, with PPAR-gamma activation, could exert a stronger effect.
Mogi
Masaki
M
Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295, Japan.
Li
Jian-Mei
JM
Tsukuda
Kana
K
Iwanami
Jun
J
Min
Li-Juan
LJ
Sakata
Akiko
A
Fujita
Teppei
T
Iwai
Masaru
M
Horiuchi
Masatsugu
M
D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage*; D001565:Benzoates / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003072:Cognition Disorders / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019808:Losartan / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D047495:PPAR gamma / Q000819:agonists*; D000077333:Telmisartan
C457499:2-chloro-5-nitrobenzanilide; D016229:Amyloid beta-Peptides; D047228:Angiotensin II Type 1 Receptor Blockers; D000813:Anilides; D001562:Benzimidazoles; D001565:Benzoates; D047495:PPAR gamma; D019808:Losartan; D000077333:Telmisartan