Document Detail

Diabetes-associated cognitive impairment is improved by a calcium channel blocker, nifedipine.
MedLine Citation:
PMID:  18195165     Owner:  NLM     Status:  MEDLINE    
Nifedipine, a calcium channel blocker, has been reported to exert pleiotropic effects on atherosclerosis, mainly through its antioxidative properties. However, the effect of the calcium channel blocker on cognitive impairment associated with type 2 diabetes mellitus is not well known. Here, we examined the possibility that a calcium channel 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 7 weeks of age exhibited impairment of the increase in avoidance rate and, moreover, exaggeration of its age-dependent decline, especially after 12 weeks of age. Oral administration of nifedipine at a nonhypotensive dose (0.001% in laboratory chow) to KK-A(y) mice from 10 weeks of age improved cognitive function. Nifedipine treatment decreased serum insulin level to one fifth of that in KK-A(y) mice without nifedipine. Moreover, nifedipine treatment significantly reduced superoxide anion production in the brain. Furthermore, treatment with nifedipine markedly reduced the mRNA level of Id-1, inhibitor of neural differentiation, in the brain hippocampus. We also observed the increase in blood flow in the brain in KK-A(y) mice with nifedipine treatment compared with nontreated mice. Taken together, our findings suggest that nifedipine ameliorates impaired cognitive function in type 2 diabetic mice, at least because of attenuation of hyperinsulinemia and superoxide production in the brain and possible upregulation of the neural differentiation-controlling gene, Id-1.
Kana Tsukuda; Masaki Mogi; Jian-Mei Li; Jun Iwanami; Li-Juan Min; Akiko Sakata; Teppei Fujita; Masaru Iwai; Masatsugu Horiuchi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-01-14
Journal Detail:
Title:  Hypertension     Volume:  51     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-24     Completed Date:  2008-02-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  528-33     Citation Subset:  IM    
Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295, Japan.
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MeSH Terms
Brain / metabolism
Calcium Channel Blockers / pharmacology*
Cerebrovascular Circulation / drug effects
Cognition / drug effects*
Cognition Disorders / etiology*,  psychology*
Diabetes Mellitus, Type 2 / blood,  psychology*
Disease Models, Animal
Hippocampus / metabolism
Inhibitor of Differentiation Protein 1 / genetics,  metabolism
Insulin / blood
Mice, Mutant Strains
Nifedipine / pharmacology*
RNA, Messenger / metabolism
Superoxides / antagonists & inhibitors
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Idb1 protein, mouse; 0/Inhibitor of Differentiation Protein 1; 0/RNA, Messenger; 11061-68-0/Insulin; 11062-77-4/Superoxides; 21829-25-4/Nifedipine

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