Site-specific induction of Fos immunoreactivity in preoptic and hypothalamic NADPH-positive neurons during glucoprivation

Neuronal nitric oxide synthase, e.g. NADPH diaphorase (NADPH-d), catalyzes formation of the free radical, nitric oxide (NO), and occurs within brain s tructures that have functional significance for energy fuel homeostasis. Th e following studies examined whether populations of NADPH-d-positive neuron s in the hypothalamus and nearby preoptic area express immunoreactivity for the nuclear transcription factor, Fos, in response to glucose substrate im balance. Eight days after bilateral ovariectomy (OVX) and subcutaneous impl antation of silastic capsules containing 30 mu g estradiol benzoate/ml, fem ale rats were injected i.p. with the glucose antimetabolite, 2-deoxy-D-gluc ose (2DG; 400 mg/kg), or the vehicle, saline. The animals were sacrificed b y transcardial perfusion 2 h after these treatments. Sections at 150-mu m i ntervals throughout preoptic area and anterior and tuberal regions of the h ypothalamus were processed for dual cytoplasmic NADPH-d enzyme activity and nuclear Fos-immunoreactivity (-ir). The glucose antimetabolite elicited ex pression of nuclear Fos-ir by NADPH-d-positive neurons in several neural st ructures, including the me-dial preoptic area, median preoptic nucleus, ant erior commissural, periventricular magnocellular supraoptic nucleus, parave ntricular nucleus, and medial part of the bed nucleus of the stria terminal is. In contrast, the extensive populations of NADPH-d-positive neurons in t he ventromedial hypothalamic nucleus and lateral hypothalamic area showed v ery little immunolabeling for Fos in response to glucoprivation. This demon stration of nuclear immunoreactivity for Fos suggests that cellular glucope nia elicits the transcriptional activation, via AP-1 regulatory sites, of m ultiple populations of hypothalamic neurons characterized by the functional capacity to generate NO, and thus that this gaseous neurotransmitter may f ulfill a role(s) in central neural mechanisms governing regulation of compe nsatory motor responses to metabolic imbalance.