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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| Format: | Article |
| Language: | English |
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Elsevier
2004-08-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996104000981 |
| _version_ | 1823934366410080256 |
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| author | M Gupta M Polinsky H Senephansiri O.C Snead E.E.W Jansen C Jakobs K.M Gibson |
| author_facet | M Gupta M Polinsky H Senephansiri O.C Snead E.E.W Jansen C Jakobs K.M Gibson |
| author_sort | M Gupta |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T22:19:44Z |
| format | Article |
| id | doaj.art-f284c5118ba140f2b6b264e8591e3b00 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-16T22:19:44Z |
| publishDate | 2004-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-f284c5118ba140f2b6b264e8591e3b002022-12-21T22:14:04ZengElsevierNeurobiology of Disease1095-953X2004-08-01163556562Seizure evolution and amino acid imbalances in murine succinate semialdehyde dehydrogenase (SSADH) deficiencyM Gupta0M Polinsky1H Senephansiri2O.C Snead3E.E.W Jansen4C Jakobs5K.M Gibson6Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA; Department of Pediatrics, Division of Neurology and The Program in Brain and Behavior, Faculty of Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; Metabolic Unit, Department of Clinical Chemistry, Vrije Universiteit Medical Center, Amsterdam, The NetherlandsDepartment of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA; Department of Pediatrics, Division of Neurology and The Program in Brain and Behavior, Faculty of Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; Metabolic Unit, Department of Clinical Chemistry, Vrije Universiteit Medical Center, Amsterdam, The NetherlandsDepartment of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA; Department of Pediatrics, Division of Neurology and The Program in Brain and Behavior, Faculty of Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; Metabolic Unit, Department of Clinical Chemistry, Vrije Universiteit Medical Center, Amsterdam, The NetherlandsDepartment of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA; Department of Pediatrics, Division of Neurology and The Program in Brain and Behavior, Faculty of Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; Metabolic Unit, Department of Clinical Chemistry, Vrije Universiteit Medical Center, Amsterdam, The NetherlandsDepartment of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA; Department of Pediatrics, Division of Neurology and The Program in Brain and Behavior, Faculty of Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; Metabolic Unit, Department of Clinical Chemistry, Vrije Universiteit Medical Center, Amsterdam, The NetherlandsDepartment of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA; Department of Pediatrics, Division of Neurology and The Program in Brain and Behavior, Faculty of Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; Metabolic Unit, Department of Clinical Chemistry, Vrije Universiteit Medical Center, Amsterdam, The NetherlandsDepartment of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA; Department of Pediatrics, Division of Neurology and The Program in Brain and Behavior, Faculty of Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; Metabolic Unit, Department of Clinical Chemistry, Vrije Universiteit Medical Center, Amsterdam, The NetherlandsMice 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.http://www.sciencedirect.com/science/article/pii/S0969996104000981EpilepsyGABAGamma-hydroxybutyric acidGlutamineSuccinic semialdehyde dehydrogenase deficiencyKnockout |
| spellingShingle | M Gupta M Polinsky H Senephansiri O.C Snead E.E.W Jansen C Jakobs K.M Gibson Seizure evolution and amino acid imbalances in murine succinate semialdehyde dehydrogenase (SSADH) deficiency Neurobiology of Disease Epilepsy GABA Gamma-hydroxybutyric acid Glutamine Succinic semialdehyde dehydrogenase deficiency Knockout |
| title | Seizure evolution and amino acid imbalances in murine succinate semialdehyde dehydrogenase (SSADH) deficiency |
| title_full | Seizure evolution and amino acid imbalances in murine succinate semialdehyde dehydrogenase (SSADH) deficiency |
| title_fullStr | Seizure evolution and amino acid imbalances in murine succinate semialdehyde dehydrogenase (SSADH) deficiency |
| title_full_unstemmed | Seizure evolution and amino acid imbalances in murine succinate semialdehyde dehydrogenase (SSADH) deficiency |
| title_short | Seizure evolution and amino acid imbalances in murine succinate semialdehyde dehydrogenase (SSADH) deficiency |
| title_sort | seizure evolution and amino acid imbalances in murine succinate semialdehyde dehydrogenase ssadh deficiency |
| topic | Epilepsy GABA Gamma-hydroxybutyric acid Glutamine Succinic semialdehyde dehydrogenase deficiency Knockout |
| url | http://www.sciencedirect.com/science/article/pii/S0969996104000981 |
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