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

Abstract

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 KD 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.

• Authors: Kirk Nylen, Jose Luis Perez Velazquez, Venus Sayed, K Michael Gibson, W M Burnham, O Carter Snead 3rd
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1790 Issue 3 Pg. 208-12 (Mar 2009) ISSN: 0006-3002 [Print] Netherlands
• PMID: 19168117 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adenosine Triphosphate
• Aldh5a1 protein, mouse
• Succinate-Semialdehyde Dehydrogenase

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Brain (enzymology, metabolism)
• Calibration
• Diet, Ketogenic
• Mice
• Mice, Knockout
• Microscopy, Electron, Transmission
• Mitochondria (enzymology, metabolism)
• Succinate-Semialdehyde Dehydrogenase (genetics, metabolism)