title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Neuroscience and Mental Health, 6535 Hill Wing, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8. kirk.nylen@utoronto.ca
authors.forename: Kirk
authors.initials: K
authors.lastname: Nylen
authors.forename: Jose Luis Perez
authors.initials: JL
authors.lastname: Velazquez
authors.forename: Venus
authors.initials: V
authors.lastname: Sayed
authors.forename: K Michael
authors.initials: KM
authors.lastname: Gibson
authors.forename: W M
authors.initials: WM
authors.lastname: Burnham
authors.forename: O Carter
authors.initials: OC
authors.lastname: Snead
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002138:Calibration; D055423:Diet, Ketogenic; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D050644:Succinate-Semialdehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*
chemical_list: D000255:Adenosine Triphosphate; C520316:Aldh5a1 protein, mouse; D050644:Succinate-Semialdehyde Dehydrogenase