Developmental Changes in Expression of GABAA Receptor Subunits α1, α2, and α3 in the Pig Brain

GABA is a major neurotransmitter in the mammalian brain. In the mature brain GABA exerts inhibitory actions via the GABA(A) receptor (GABA(A)R); however, in the immature brain GABA provides much of the excitatory drive. We examined the expression of 3 predominant GABA(A) alpha-subunit proteins in the pig brain at various pre- and postnatal ages. Brain tissue was collected from piglets born via caesarean section at preterm ages 91, 97,100, and 104 days' gestational age (GA), at term equivalent (114 days' GA, caesarean section) and at term, postnatal day 0 (P0) (spontaneous delivery, term = 115 days). Tissue was obtained from piglets at P4 and P7. Adult tissue from sows was collected postmortem after caesarean section. In all cortical regions and basal ganglia (1) alpha(3) exhibited a significant increase in protein expression at 100 days' GA, (2) alpha(3) expression decreased with age after 100 days' GA, (3) alpha(1) increased with age, with peak expression at P7 in cortices, hippocampus, and thalamus, and (4) alpha(2) protein expression remained relatively constant across the ages examined. The subunit expression of alpha(3) was most abundant at preterm ages, with alpha(1) the predominant subunit expressed postna-tally. Immunofluorescent labelling revealed alpha(1) expression on the somatic membranes of pyramidal cells in the cortex and hippocampus, and in the cerebellar Purkinje cells. Positive alpha(3) labelling was apparent on interneurones in the cortex and hippocampus.The switch between dominant alpha-subunits may coincide with the functional change in GAB(A)ergic neurotransmission from excitation to inhibition. Brain growth in the pig closely reflects that in the term human, making the pig a valuable non-primate model for studying development and the effects of insults on the perinatal brain. (C) 2017 S. Karger AG, Basel