REDUCTION OF FUNCTIONAL GABA_A RECEPTOR EXPRESSION IN THE NEOCORTEX OF EL MICE

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There is extensive evidence indicating a crucial role for γ-aminobutyric acid (GABA) in epileptogenesis. The El (epilepsy-like) mouse is an epilepsy model developed from the ddY mouse and is very susceptible to seizure. El mice have been found to exhibit a decrease in GABA-mediated inhibition. However, previous studies remained nuclear about relationship between the GABA receptor function and epileptogenesis. In the present study, we investigated the GABA_A receptor gene expression and function in the neocortex of unstimulated El mice and ddY control mice (18-20 weeks old).1) Northern blot analysis showed 30% decrease in GABA_A receptor α1 subunit messenger RNA (mRNA) level in El mice, compared to ddY mice. On the other hand, β2 and γ2 subunit mRNA levels did not show any significant differences.2) GABA_A receptor functions were analyzed by the measurement of GABA-induced currents using Xenopus oocytes expression system. The maximal GABA-induced currents obtained from oocytes injected with neocortex mRNA of El mice, were significantly smaller than those obtained from oocytes injected with mRNA of ddY mice.3) Extracellular recordings from the neocortex slices using single-pulse configuration showed significant difference in the GABA_A receptor antagonist (bicuculline: BMI and picrotoxin:PTX)-induced changes of field significant decrease in the BMI and PTX-induced changes of the amplitude of field potentials in El(-) mice.These results suggest that, in the neocortex of El(-) mice, there is a decrease in GABA_A receptor expression and recurrent GABAergic inhibition, which may be related to the epileptogenesis in the El strain.