Prenatal GABAB1 and GABAB2 receptors: Cellular and subcellular organelle localization in early fetal rat cortical neurons

Abstract

Gamma-aminobutyric acid (GABA)(B) receptors appear to influence developmental events, depending on whether they are found at a synapse or in extrasynaptic areas. Little, if anything, is known as to the cellular and subcellular localization of GABA(B1) and GABA(B2) receptors during early fetal development. We used Western blots, immunohistochemistry, and postembedding immunoelectronmicroscopy to investigate fetal rat brain expression and distribution of these receptor proteins. GABA(B1) is expressed as early as gestational day (GD) 11.5 and 12.5, with immunoreactivity found in the all neuroepithelium, and a high expression in the mantel zone and the cortical area's plate; no immunolabeling for GABA(B2) receptor was observed. Our immunogold studies define a pattern of early GABA(B1) receptor protein in dendrite processes, endoplasmic reticulum, and axon terminals of the cortical neuroepithelium on GD 11.5. On GD 12.5, GABA(B1) receptor immunogold was found in dendrite processes, spines and tree, axon terminals, mitochondria, and intracellular organelles of the cortical neuroepithelium. No synapse formation was apparent as no synaptophysin could be found on either GD 11.5 or 12.5. We suggest that GABA(B1) has a functional role in the early fetal brain during neuronal proliferation and migration, and that it is different from the established functional GABA(B) receptor.