DEVELOPMENT OF GABA (A) RECEPTOR ALPHA1 AND GAMMA2 SUBUNIT IN HUMAN TEMPORAL LOBE, HIPPOCAMPUS AND BASAL GANGLIA

Objectives: To examine the development of GABA (A) receptor alpha1 subunit (GABARA1) and gamma2 subunit (GABARG2) in human brain. Recently, the genes encoding GABARA1 and GABARG2 were found to be associated with age dependent epilepsy. Nevertheless, developmental and spatial changes of both subunits expression in human brain surprisingly had not been examined.

Methods: Using immunohistochemistry, we observed GABARA1 and GABARG2 in the temporal lobe, hippocampus and basal ganglia of specimens obtained from 21 fetuses/subjects who died at 22 gestation weeks (GW) to adulthood. The specimens were stained with the corresponding antibodies followed by avidin-biotin visualization.

Results: There were unique developmental changes of GABARA1 and GABARG2 in the region examined. In the temporal cortex, both subunits appeared in the pyramidal cells layer from 22GW. GABARA1 increased in the pyramidal cell layer from early fetal period and showed a transint increase in late fetal period. GABARG2 reached the adult level by 38 GW. In hippocampal pyramidal cells, both subunits were already observed from 22 GW mainly in CA2–3, whereas GABARG2 was observed predominantly in CA3 followed by GABARA1. Furthermore, transient increase of GABARA1 was found from 29 GW to 4 months in the granular cell layer of the hippocampus, from 29 GW to 4 months in the cortical pyramidal cell layer and from birth to 5 years of age in the putamen. In contrast, GABARG2 increased developmentally in every region. Conclusion: Thus gradual or transient increase ofGABARA1 and GABARG2 was found in every region at different age. These developmental changes in the expression of these subunits may contribute to the age dependency of certain epilepsy syndromes where deficient GABARA1 and GABARG2 are involved. Further developmental studies are necessary in human epilepsy patients and animal models.