GABA mediates steroid-induced astrocyte differentiation in the neonatal rat hypothalamus

Our previous work has demonstrated that astrocytes in the developing arcuate nucleus of the rat hypothalamus are sexually dimorphic as a result of differential exposure to oestradiol. Moreover, our experiments in neonatal rats suggest an absence of oestrogen receptors (ER) in arcuate nucleus astrocytes in vivo. This, along with the conspicuous lack of evidence in the literature confirming the presence of ER in arcuate nucleus astrocytes of the neonatal rat brain, led us to question the mechanism by which oestrogen induces changes in arcuate nucleus astrocyte morphology. Based on our previous findings that oestradiol increases gamma-aminobutyric acid (GABA) levels in the neonatal rat arcuate, we hypothesize that GABA is released from neighbouring oestrogen-sensitive neurones and alters arcuate nucleus astrocyte morphology. Here, we report that in vivo reduction of GABA synthesis in the neonatal rat brain by antisense oligodeoxynucleotides to glutamic acid decarboxylase prevented gonadal steroid-induced astrocyte differentiation in males and testosterone-treated females. Conversely, activation of GABAA receptors with the agonist muscimol increased astrocyte differentiation in females in the absence of gonadal steroids. Given that GABA is made only in neurones and that its synthesis is increased by oestradiol, we conclude that it acts as a diffusible factor inducing the differentiation of neighbouring astrocytes.