Seizure evolution and amino acid imbalances in murine succinate semialdehyde dehydrogenase (SSADH) deficiency

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...

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Bibliographic Details
Published in:Neurobiology of disease 2004-08, Vol.16 (3), p.556-562
Main Authors: Gupta, M, Polinsky, M, Senephansiri, H, Snead, O.C, Jansen, E.E.W, Jakobs, C, Gibson, K.M
Format: Article
Language:English
Subjects:
Aldehyde Oxidoreductases - deficiency
Aldehyde Oxidoreductases - genetics
Amino Acids - metabolism
Animals
Brain - metabolism
Brain - physiopathology
Disease Models, Animal
Disinhibition
Epilepsy
Epilepsy - physiopathology
GABA
gamma-Aminobutyric Acid - metabolism
Gamma-hydroxybutyric acid
Glutamic Acid - metabolism
Glutamine
Glutamine - metabolism
Knockout
Mice
Mice, Inbred C57BL
Mice, Knockout
Neural Inhibition
Succinate-Semialdehyde Dehydrogenase
Succinic semialdehyde dehydrogenase deficiency
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Summary: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.
ISSN:0969-9961
1095-953X
DOI:10.1016/j.nbd.2004.04.008