title: Ameliorative effects of telmisartan on the inflammatory response and impaired spatial memory in a rat model of Alzheimer's disease incorporating additional cerebrovascular disease factors.
abstract: Telmisartan, an angiotensin type 1 receptor blocker, is used in the management of hypertension to control blood pressure. In addition, telmisartan has a partial agonistic effect on peroxisome proliferator activated receptor γ (PPARγ). Recently, the effects of telmisartan on spatial memory or the inflammatory response were monitored in a mouse model of Alzheimer's disease (AD). However, to date, no studies have investigated the ameliorative effects of telmisartan on impaired spatial memory and the inflammatory response in an AD animal model incorporating additional cerebrovascular disease factors. In this study, we examined the effect of telmisartan on spatial memory impairment and the inflammatory response in a rat model of AD incorporating additional cerebrovascular disease factors. Rats were subjected to cerebral ischemia and an intracerebroventricular injection of oligomeric or aggregated amyloid-β (Aβ). Oral administration of telmisartan (0.3, 1, 3 mg/kg/d) seven days after ischemia and Aβ treatment resulted in better performance in the eight arm radial maze task in a dose-dependent manner. Telmisartan also reduced tumor necrosis factor α mRNA expression in the hippocampal region of rats with impaired spatial memory. These effects of telmisartan were antagonized by GW9662, an antagonist of PPARγ. These results suggest that telmisartan has ameliorative effects on the impairment of spatial memory in a rat model of AD incorporating additional cerebrovascular disease factors via its anti-inflammatory effect.
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Fukuoka University, 7–45–1 Nanakuma, Jonan-ku, Fukuoka 814–0180, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Shindo
authors.forename: Kotaro
authors.initials: K
authors.lastname: Takasaki
authors.forename: Kanako
authors.initials: K
authors.lastname: Uchida
authors.forename: Rika
authors.initials: R
authors.lastname: Onimura
authors.forename: Kaori
authors.initials: K
authors.lastname: Kubota
authors.forename: Naoki
authors.initials: N
authors.lastname: Uchida
authors.forename: Keiichi
authors.initials: K
authors.lastname: Irie
authors.forename: Shutaro
authors.initials: S
authors.lastname: Katsurabayashi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mishima
authors.forename: Ryoji
authors.initials: R
authors.lastname: Nishimura
authors.forename: Michihiro
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Katsunori
authors.initials: K
authors.lastname: Iwasaki
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D000682:Amyloid / Q000009:adverse effects; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001565:Benzoates / Q000494:pharmacology / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D002561:Cerebrovascular Disorders / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D054022:Cerebrum / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077333:Telmisartan; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000682:Amyloid; D047228:Angiotensin II Type 1 Receptor Blockers; D000813:Anilides; D000893:Anti-Inflammatory Agents; D001562:Benzimidazoles; D001565:Benzoates; D047495:PPAR gamma; D014409:Tumor Necrosis Factor-alpha; D000077333:Telmisartan