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

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概要

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• 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.

著者

• Irie Keiichi

  Department Of Neuropharmacology Faculty Of Pharmaceutical Sciences Fukuoka University

• Uchida Kanako

  Department Of Applied Biological Chemistry Graduate School Of Agricultural And Life Sciences The Uni

• Nishimura Ryoji

  Department Of Psychiatry Faculty Of Medicine Fukuoka University

• Iwasaki Katsunori

  Department Of Mathematical Sciences The University Of Tokyo

• Kubota Kaori

  Department Of Astronomy Kyoto University

• Mishima Kenichi

  Department Of Chemical Engineering Faculty Of Engineering Fukuoka University

• Fujiwara Michihiro

  Department Of Neuroparmacology Faculty Of Pharmaceutical Sciences Fukuoka University

• Shindo Taro

  Department Of Psychiatry Fukuoka University School Of Medicine Fukuoka University

• Uchida Naoki

  Department Of Psychiatry Fukuoka University School Of Medicine Fukuoka University

• Katsurabayashi Shutaro

  Department Of Neuropharmacology Faculty Of Pharmaceutical Science Fukuoka University

• Takasaki Kotaro

  Department Of Neuropharmacology Faculty Of Pharmaceutical Science Fukuoka University

• Onimura Rika

  Department of Neuropharmacology, Faculty of Pharmaceutical Science, Fukuoka University

• Shindo Taro

  Department of Psychiatry, Faculty of Medicine, Fukuoka University

• Irie Keiichi

  Department of Neuropharmacology, Faculty of Pharmaceutical Science, Fukuoka University

• UCHIDA Naoki

  Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University

• Uchida Naoki

  Department of Psychiatry, Faculty of Medicine, Fukuoka University

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