title: Seizure evolution and amino acid imbalances in murine succinate semialdehyde dehydrogenase (SSADH) deficiency.
abstract: Mice with targeted deletion of the GABA catabolic enzyme succinic semialdehyde dehydrogenase (SSADH) manifest lethal tonic-clonic seizures, amenable to pharmacologic rescue, at 3-4 weeks of life. In the current report, we characterized amino acid profiles in SSADH(-/-) brain utilizing whole brain and regional extracts (frontal and parietal cortex, hippocampus, and cerebellum) to develop hypotheses concerning epileptogenesis. Of 35 amino acids quantified, we found significant dysregulation in SSADH(-/-) mice for 11 (GABA, glutamate, glutamine, alanine, aspartate, serine, taurine, cystathionine, methionine, homocarnosine, and arginine) as compared to age-matched littermates both before, and following, the period of generalized convulsive seizures and status epilepticus. Our results reveal imbalanced amino acid levels potentially involved in the transition from absence seizures to generalized convulsive seizures resulting in SSADH(-/-) mice. We conclude that the SSADH(-/-) mouse represents a unique epileptic model with the potential to reveal novel aspects of excitatory/inhibitory interactions in the genesis of seizures.
authors.affiliation: Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97201, USA.
authors.forename: M
authors.initials: M
authors.lastname: Gupta
authors.forename: M
authors.initials: M
authors.lastname: Polinsky
authors.forename: H
authors.initials: H
authors.lastname: Senephansiri
authors.forename: O C
authors.initials: OC
authors.lastname: Snead
authors.forename: E E W
authors.initials: EE
authors.lastname: Jansen
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
authors.forename: K M
authors.initials: KM
authors.lastname: Gibson
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000172:deficiency / Q000235:genetics*; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000503:physiopathology*; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009433:Neural Inhibition; D050644:Succinate-Semialdehyde Dehydrogenase; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000596:Amino Acids; D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000445:Aldehyde Oxidoreductases; D050644:Succinate-Semialdehyde Dehydrogenase