Status epilepticus in mice deficient for succinate semialdehyde dehydrogenase: GABAA receptor-mediated mechanisms.

摘要: The epilepsy that occurs in SSADH deficiency has a seizure phenotype similar to occurring the SSADH(-/-) mouse. We examined expression and function of GABA(A) receptor (GABA(A)R) SSADH-deficient mice. A selective decrease binding [(35)S]tert-butylbicyclophosphorothionate was observed mice at postnatal day 7 progressive until third week life when, nadir decreased binding, generalized convulsive seizures emerged rapidly evolved into status epilepticus. also substantial downregulation beta(2) subunit GABA(A)R, reduction GABA(A)-mediated inhibitory postsynaptic potentials, augmented population spikes recorded from hippocampal slices. mouse model represents powerful investigative tool for understanding pathophysiology associated with human deficiency. These data raise possibility dysfunction GABA(A)R may be involved development SSDAH-deficient Elucidation precise fundamental mechanisms perturbation GABA(A)R-mediated could lead novel treatment modalities designed reduce neurological morbidity children