The effects of a ketogenic diet on ATP concentrations and the number of hippocampal mitochondria in Aldh5a1-/- mice

被引：51

作者：

Nylen, Kirk ^{[1
,3
,4
]}

Velazquez, Jose Luis Perez ^{[2
,4
]}

Sayed, Venus ^{[5
]}

Gibson, K. Michael ^{[6
,7
,8
]}

Burnham, W. M. ^{[3
,4
]}

Snead, O. Carter, III ^{[2
,3
,4
]}

机构：

[1] Hosp Sick Children, Neurosci & Mental Hlth Div Neurol, Toronto, ON M5G 1X8, Canada

[2] Hosp Sick Children, Div Neurol, Toronto, ON M5G 1X8, Canada

[3] Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A1, Canada

[4] Univ Toronto, Epilepsy Res Program, Toronto, ON M5S 1A1, Canada

[5] Univ Toronto, Dept Human Biol, Toronto, ON M5S 1A1, Canada

[6] Univ Pittsburgh, Sch Med, Div Med Genet, Dept Pediat, Pittsburgh, PA USA

[7] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA

[8] Univ Pittsburgh, Sch Med, Dept Human Genet, Childrens Hosp, Pittsburgh, PA USA

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2009年 / 1790卷 / 03期

基金：

加拿大健康研究院;

关键词：

Ketogenic diet; Succinic semialdehyde dehydrogenase deficiency; Mitochondria; ATP; Hippocampus; SEMIALDEHYDE DEHYDROGENASE-DEFICIENCY; KETONE-BODIES; MODEL; METABOLISM; DYSFUNCTION; SEIZURES;

D O I：

10.1016/j.bbagen.2008.12.005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Background: Succinic semialdehyde dehydrogenase (SSADH) deficiency is an inborn error of GABA metabolism characterized clinically by ataxia, psychomotor retardation and seizures. A mouse model of SSADH deficiency, the Aldh5a1(-/-) mouse, has been used to study the pathophysiology and treatment of this disorder. Recent work from our group has shown that the ketogenic diet (KD) is effective in normalizing the Aldh5a1(-/-) phenotype, although the mechanism of the effect remains unclear. Methods: Here, we examine the effects of a KD on the number of hippocampal mitochondria as well as on ATP levels in hippocampus. Electron microscopy was performed to determine the number of mitochondria in the hippocampus of Aldh5a1(-/-) mice. Adenosine triphosphate (ATP) levels were measured in hippocampal extracts. Results: Our results show that the KID increases the number of mitochondria in Aldh5a1(-/-) mice. We also show that Aldh5a1(-/-) mice have significant reductions in hippocampal ATP levels as compared to controls, and that the KD restores ATP in mutant mice to normal levels. General significance: Taken together, our data suggest that the KD's actions on brain mitochondria may play a role in the diet's ability to treat murine SSADH deficiency.. (C) 2009 Elsevier B.V. All rights reserved.

引用

页码：208 / 212

页数：5

共 21 条

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Yokoyama, Y ;

Inoue, A ;

Note, R ;

Kaneko, T .

MATERIALS TRANSACTIONS JIM, 1998, 39 (02) :237-244

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