Affiliations: [a] Departments of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Chuo-ku, Kumamoto, Japan | [b] Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan | [c] Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, Chuo-ku, Kumamoto, Japan
Correspondence:
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Correspondence to: Shokei Kim-Mitsuyama, MD, PhD, FAHA, Departments of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjyo, Chuo-ku, Kumamoto 860 8556, Japan. Tel: +81 96 373 5082; Fax: +81 96 373 5082; E-mail: mitsuyam@gpo.kumamoto-u.ac.jp.
Abstract: This work was performed to test our hypothesis that angiotensin-(1–7) can ameliorate cognitive impairment and cerebrovascular reactivity in 5XFAD mice, a useful model of Alzheimer’s disease. 5XFAD mice received intracerebroventricular infusion of (1) vehicle, (2) angiotensin-(1–7), or (3) angiotensin-(1–7)+A779, a specific Mas receptor antagonist, for 4 weeks. Angiotensin-(1–7), through Mas receptor, significantly ameliorated cognitive impairment in 5XFAD mice. As estimated by acetazolamide-induced increase in cerebral blood flow, angiotensin-(1–7), through Mas receptor, enhanced cerebrovascular reactivity in 5XFAD mice. In conclusion, angiotensin-(1–7)/Mas receptor axis improves cognitive function and cerebrovascular function in a mouse model of Alzheimer’s disease.
Keywords: Acetazolamide, angiotensin-(1–7), cognitive function, Mas receptor, vascular reactivity, water maze test
