Amelioration of cognitive impairment in the type-2 diabetic mouse by the angiotensin II type-1 receptor blocker candesartan.

Amelioration of cognitive impairment in the type-2 diabetic mouse by the angiotensin II type-1 receptor blocker candesartan. Research Abstract Details 

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Amelioration of cognitive impairment in the type-2 diabetic mouse by the angiotensin II type-1 receptor blocker candesartan. Abstract Text:

Kana Tsukuda,Masaki Mogi,Jian-Mei Li,Jun Iwanami,Li-Juan Min,Akiko Sakata,Teppei Fujita,Masaru Iwai,Masatsugu Horiuchi,

Angiotensin II type-1 receptor blockers are widely used with the expectation of prevention of stroke, potential effects to ameliorate of type-2 diabetes, which seems to be closely associated with the impairment of cognitive function in humans. Recently, we have reported that an angiotensin II type-1 receptor blocker prevented cognitive impairment in mice after focal cerebral ischemia, at least partly through an angiotensin II type-2 receptor-mediated increase in a neuroprotective factor, methyl methanesulfonate sensitive-2. Here, we examined the possibility that an angiotensin II type-1 receptor blocker could improve cognitive function in a type-2 diabetic mouse model, KK-A(y). KK-A(y) mice subjected to 20 trials of a passive avoidance task every week from 8 weeks exhibited a significantly impaired avoidance rate, and moreover, its age-dependent decline, especially after 14 weeks of age, compared with age-matched C57BL6 mice. Oral administration of candesartan at a nonhypotensive dose (0.005% in laboratory chow) in KK-A(y) mice improved cognitive function and inhibited the impairment of cognitive decline. Methyl methanesulfonate sensitive-2 expression in the brain was lower in KK-A(y) mice than in C57BL6 mice. Treatment with candesartan markedly increased mRNA expression of angiotensin II type-2 receptor and methyl methanesulfonate sensitive-2 in the brain in KK-A(y) mice, determined by quantitative RT-PCR. In KK-A(y) mice treated with candesartan, age-dependent increases in blood glucose and insulin were significantly suppressed. Our results suggest that candesartan ameliorates the impaired cognitive function in type-2 diabetes mice, at least because of an increased expression of methyl methanesulfonate sensitive-2, a neuroprotective factor, in addition to improvement of glucose intolerance.

Amelioration of cognitive impairment in the type-2 diabetic mouse by the angiotensin II type-1 receptor blocker candesartan. Publishing Authors By Initials

K Tsukuda,M Mogi,JM Li,J Iwanami,LJ Min,A Sakata,T Fujita,M Iwai,M Horiuchi,

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Amelioration of cognitive impairment in the type-2 diabetic mouse by the angiotensin II type-1 receptor blocker candesartan. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Hypertension

VOLUME: 50

Page Numbers: 1099-105

Journal Abbreviation: Hypertension

ISSN: 1524-4563

DAY: 29

MONTH: 10

YEAR: 2007

Amelioration of cognitive impairment in the type-2 diabetic mouse by the angiotensin II type-1 receptor blocker candesartan. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Amelioration of cognitive impairment in the type-2 diabetic mouse by the angiotensin II type-1 receptor blocker candesartan.

AFFILIATION: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295, Japan.

Country: United States

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MEDLINETA: Hypertension

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