Developmental changes in the expression of GABAA receptor alpha 1 and gamma 2 subunits in human temporal lobe, hippocampus and basal ganglia: an implication for consideration on age-related epilepsy.

Mutations of genes encoding GABA(A) receptor alpha 1 (GABARA1) and gamma 2 subunit (GABARG2) are associated with age-dependent epilepsy. The development of the subunits expression may be related to the age-dependency of epilepsy. Nevertheless, developmental and spatial changes in expression of GABA(A) receptors have not been examined in the human brain. Using immunohistochemistry, we examined the development of GABARA1 and GABARG2 in the human temporal lobe, hippocampus and basal ganglia in specimens obtained from 21 fetuses/subjects who died aged 22 gestation weeks (GW) to 75 years. Unique developmental changes of GABARA1 and GABARG2 were recorded in each region. In hippocampal pyramidal cells, GABARA1 was already found from 22 GW mainly on CA2-3, whereas GABARG2 was expressed later than GABARA1 predominantly in CA3. In the temporal cortex, both subunits appeared in the pyramidal cells layer from 22 GW, while GABARA1 and GABARG2 expression was increased from 29 to 38 GW, respectively. Furthermore, transient increase of GABARA1 was detected in the granular cell layer of the hippocampus from 29 GW to 4 months, in the cortical pyramidal cell layer from 29 to 40 GW, and in the putamen from birth to 5 years of age. Thus gradual or transient increase of GABARA1 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 in some epilepsy syndromes where deficiency of GABARA1 and GABARG2 is involved.