Hypothalamic orexin-A-immunpositive neurons express Fos in response to central glucopenia.

Reports that glucose antimetabolite treatment elicits hyperphagia and hyperglycemia suggest that decreased oxidation of this energy substrate elicits compensatory responses that enhance cellular fuel availability. Neurons in the lateral hypothalamic area (LHA) synthesize the orectic neuropeptide, orexin-A (ORX-A). The present study evaluated the functional responsiveness of orexinergic neurons to glucopenia by investigating whether these cells express the genomic regulatory protein, Fos, in response to glucoprivation. Adult male rats were sacrificed 2 h after i.p. (400 mg/kg) or intracerebroventricular (i.c.v.; 100 μg) administration of the antimetabolite, 2-deoxy-D-glucose (2DG) or saline. Sections through the LHA, from the level of the paraventricular nucleus (PVN) to the posterior hypothalamic area (PHA), were processed by dual-label immunocytochemistry for Fos- and OXY-A-immunoreac-tivity (-ir). Although orexinergic neurons expressed negligible Fos-ir following vehicle administration, dual-labeled ORX-A neurons were observed in the LHA, as well as the dorsomedial hypothalamic nucleus (DMN) and PHA, in both drug-treated groups. Bilateral cell counts from representative levels of the LHA, DMN, and PHA showed that in each structure, a greater proportion of ORX-A neurons were immunostained for Fos in response to systemic than following i.c.v. treatment with 2DG. These results provide evidence for the transcriptional activation of hypothalamic ORX-A neurons by diminished glucose availability, data that suggest that these cells may function within central pathways that govern adaptive responses to deficits of this substrate fuel. The findings also support the view that a proportion of this phenotypic population is responsive to glucoprivic stimuli of central origin.