RESUMEN
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.