Hindbrain neuroglucopenia elicits site-specific transcriptional activation of glutamate decarboxylase-immunopositive neurons in the septopreoptic area of female rat brain.

Recent studies implicate the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), in septopreoptic (SPO) mechanisms that suppress preovulatory pituitary luteinizing hormone (LH) secretion during neuroglucopenia. Since Fos immunolabeling of the SPO of rats treated by caudal fourth ventricular (CV4) administration of the glucose antimetabolite, 5-thioglucose (5TG), parallels the distribution of GABA neuronal perikarya, the current studies investigated the genomic responsiveness of neuroanatomically-defined populations of glutamate decarboxylase (GAD)-immunoreactive (-ir) neurons in this region of the brain to hindbrain glucoprivation. In lieu of reports that CV4 5TG enhances SPO GABA turnover via mu opioid receptor (mu-R)-dependent mechanisms and evidence that GAD- and mu-R-ir are codistributed within the SPO, patterns of cellular colocalization of these antigens were also evaluated here. Neural tissue was obtained from groups of steroid-primed ovariectomized female rats 2 h after CV4 injection of vehicle or 5TG. Neuronal cell bodies in the lateral and medial septum, medial (MPN) and median preoptic nuclei (MEPO), and rostral medial preoptic area (rMPO) were immunostained for cytoplasmic GAD-ir, but only GAD-reactive neurons in the rMPO and MEPO exhibited robust nuclear colabeling for Fos in response to 5TG. SPO GABA neurons in the vehicle-treated controls were uniformly Fos-ir-negative. Dual immunolabeling for GAD- and mu-R revealed approximately 52% and 36% colabeling of this phenotype in the MEPO and MPN, and colocalization of lesser magnitude (18%) in the rMPO. These results demonstrate site-specific genomic activation of GABAergic neurons in the female rat SPO by CV4 glucose antimetabolite administration, and implicate MEPO and rMPO GABA cell populations in neural pathways that mediate regulatory effects of hindbrain glucoprivic signaling on CNS functions, including inhibition of the steroid positive feedback-activated gonadotropin-releasing hormone/LH neuroendocrine axis. The current studies also support the view that a proportion of neuroglucoprivic-sensitive GABA neurons in the MEPO and rMPO may be direct substrates for mu-R ligand modulatory actions during this state of central substrate imbalance.