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

Reports that glucose antimetabolite treatment elicits hyperphagia and hyper glycemia 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, or exin-A (ORX-A). The present study evaluated the functional responsiveness o f orexinergic neurons to glucopenia by investigating whether these cells ex press the genomic regulatory protein, Fos, in response to glucoprivation. A dult male rats were sacrificed 2 h after i.p. (400 mg/kg) or intracerebrove ntricular (i.c.v.; 100 mug) administration of the antimetabolite, 2-deoxy-D -glucose (2DG) or saline. Sections through the LHA, from the level of the p araventricular nucleus (PVN) to the posterior hypothalamic area (PHA), were processed by dual-label immunocytochemistry for Fos- and OXY-A-immunoreact ivity (-ir). Although orexinergic neurons expressed negligible Fos-ir follo wing vehicle administration, dual-labeled ORX-A neurons were observed in th e LHA, as well as the dorsomedial hypothalamic nucleus (DMN) and PHA, in bo th 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 fo llowing i.c.v. treatment with 2DG. These results provide evidence for the t ranscriptional activation of hypothalamic ORX-A neurons by diminished gluco se availability, data that suggest that these cells may function within cen tral pathways that govern adaptive responses to deficits of this substrate fuel. The findings also support the view that a proportion of this phenotyp ic population is responsive to glucoprivic stimuli of central origin. Neuro Report 12:531-534 (C) 2001 Lippincott Williams & Wilkins.