Developmental Expression and Distribution of GABA(A) Receptor alpha(1)-, alpha(3)- and beta(2)-Subunits in Pig Brain

作者：Kalanjati Viskasari P; Miller Stephanie M; Ireland Zoe; Colditz Paul B; Bjorkman Stella T^*

来源：Developmental Neuroscience, 2011, 33(2): 99-109.

DOI：10.1159/000326630

• GABA
• Developing brain
• Perinatal pig brain
• Excitotoxicity
• Seizure

The principal function of the gamma-aminobutyric acid (GABA) system in the adult brain is inhibition; however, in the neonatal brain, GABA provides much of the excitatory drive. As the brain develops, transmembrane chloride gradients change and the inhibitory role of GABA is initiated and continues throughout juvenile and adult life. Previous studies have shown that GABA(A) receptor subunit expression is developmentally regulated, and it is thought that the change in GABA function from excitation to inhibition corresponds to the changeover in expression of 'immature' to 'mature' subunit isoforms. We examined the protein expression pattern and distribution of GABA type A (GABA(A)) receptor alpha(1)-, alpha(3)- and beta(2)-subunits in the parietal cortex and hippocampus of the developing piglet brain. Four perinatal ages were studied; 14 days preterm (P-14), 10 days preterm (P-10), day of birth (P0) and at postnatal day 7 (P7). Animals were obtained by either caesarean section or spontaneous birth. Protein expression levels and subunit localization were analysed by Western blotting and immunohistochemistry, respectively. In the cortex and hippocampus, GABA(A) receptor alpha(1)-subunit showed greatest expression at P7 when compared to all other age groups (p < 0.05). In contrast, alpha(3) expression in the cortex was elevated in preterm brain, peaking at P0, followed by a significant reduction by P7 (p < 0.05); a similar trend was observed in the hippocampus. GABA(A) receptor beta(2)-subunit protein expression appeared relatively constant across all time points studied in both the cortex and hippocampus. Immunolabelling of the alpha(1)-, alpha(3)- and beta(2)-subunits was observed throughout all cortical layers at every age. GABA(A) receptor alpha(3)-subunit appeared to show specific localization to layers V and VI whilst labelling for the beta(2)-subunit was observed in layer IV. In the hippocampus of all animals, the alpha(1)- and beta(2)-subunits were shown to immunolabel various cells and processes in the dentate gyrus (DG), CA1 and CA3; the alpha(3)-subunit was barely observed except at the stratum moleculare of the DG. We report for the first time the ontogenesis of GABA(A) receptor subunits alpha(1), alpha(3) and beta(2) in the perinatal pig brain.

• 出版日期2011