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

Abstract

GABA is a major neurotransmitter in the mammalian brain. In the mature brain GABA exerts inhibitory actions via the GABA_A receptor (GABA_AR); however, in the immature brain GABA provides much of the excitatory drive. We examined the expression of 3 predominant GABA_A α-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) α₃ exhibited a significant increase in protein expression at 100 days' GA, (2) α₃ expression decreased with age after 100 days' GA, (3) α₁ increased with age, with peak expression at P7 in cortices, hippocampus, and thalamus, and (4) α₂ protein expression remained relatively constant across the ages examined. The subunit expression of α₃ was most abundant at preterm ages, with α₁ the predominant subunit expressed postnatally. Immunofluorescent labelling revealed α₁ expression on the somatic membranes of pyramidal cells in the cortex and hippocampus, and in the cerebellar Purkinje cells. Positive α₃ labelling was apparent on interneurones in the cortex and hippocampus. The switch between dominant α-subunits may coincide with the functional change in GABAergic 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.

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