Developmental Changes in GABA_A Receptor Subunit Composition Within the Gonadotrophin‐Releasing Hormone‐1 Neuronal System

Abstract

It is becoming increasingly evident that GABA plays an important role in the regulation of gonadotrophin-releasing hormone (GnRH)-1 neurones via the GABAA receptor. The aim of the present study was to characterise expression of the GABAA receptor within the GnRH-1 system across development. The expression pattern of five GABAAalpha subunits and one GABAAbeta subunit was first examined within individual GnRH-1 neurones by the polymerase chain reaction. A significant increase in the expression of GABAAalpha2 and a significant decrease in the expression of GABAAalpha6 over time were found. Of the other subunits examined, two (alpha1 and alpha3) showed no differences in expression and two (alpha4 and beta3) showed variable low incidence of expression. Given the reciprocal relationship of alpha2 and alpha6 expression, we hypothesised that there is a developmental switch in the expression of these subunits in GnRH-1 neurones. To investigate this hypothesis, single- and double-label immunocytochemistry for GABAAalpha2 and alpha6 and GnRH-1 was performed in tissue from ages E12.5 to adulthood, as well as in nasal explants. We show that GABAAalpha2 and alpha6 are present in the GnRH-1 neuronal system both in vivo and in vitro and that the levels of expression are altered as a function of age.

The effects of prenatal H1N1 infection at E16 on FMRP, glutamate, GABA, and reelin signaling systems in developing murine cerebellum

“…GABA A receptors are ligand-gated chloride channels consisting of five subunits and are responsible for mediating fast synaptic inhibition (Farrant and Nusser, 2005). The expression patterns we observed for GABA A receptor subunits α1, α2, β2, β3, and δ in the control mouse cerebellum are supported by previous results in various normal rodent brain regions (Chang et al, 1995; Laurie et al, 1992; Liu and Wong-Riley, 2006; Temple and Wray, 2005; Zdilar et al, 1992). However, in contrast to our data, Laurie et al (1992) found little to no signal for the α5 subunit in rat cerebellum.…”

“…Previous reports from multiple laboratories have evaluated mRNA profiles for Reelin, Fmr1, glutamate and GABA A receptor subunits in normal rodent brain (Catania et al, 1994; Chang et al, 1995; Laurie et al, 1992; Liu and Wong-Ridley, 2006; Lu et al, 2004; Muñoz et al, 1999; Popp et al, 2009; Richard et al, 2008; Singh and Prasad, 2008; Temple and Wray, 2005; Zdilar et al, 1992). We sought to verify and correlate these earlier reports with protein data.…”

Chapter 2 Hypothalamic Neural Systems Controlling the Female Reproductive Life Cycle

“…Temple and Wray (Temple and Wray, 2005) examined embryonic day (E) 11.5 mouse nasal explants at various time points (culture day 3.5, 7, 14, and 28) to determine the expression patterns of the GABA A R subunits α1–4, α6, and β3 using PCR analysis, and to ascertain their changes as a function of age. Some significant changes in expression were seen, suggesting alterations in the receptor stoichiometry during development in vitro .…”

The Effects of GABA on Embryonic Gonadotropin-Releasing Hormone Neurons in Rat Hypothalamic Primary Culture

“…For example, electrophysiological studies have demonstrated that GABA acts on juvenile and adult GnRH neurons in hypothalamus and olfactory placodederived GnRH neurons [16,18,25]. GABA-A receptor subunit mRNA is expressed in olfactory placode-derived GnRH neurons [26] and postnatal [27], juveniles, and adult GnRH neurons [28], and GABA-A receptor immunoreactivity has been detected in migrating GnRH neurons [21]. In addition, it has been reported that GABA-B receptor mRNA is also expressed in olfactory placode-derived GnRH neurons [29], and GABA-B receptor immunoreactivity has been detected in adult sheep GnRH neurons [30].…”