Glucoprivation increases expression of neuropeptide Y mRNA in hindbrain neurons that innervate the hypothalamus.

The hypothalamus is jointly innervated by hindbrain and hypothalamic neuropeptide Y (NPY) cell bodies. While the specific roles of these distinct sources of innervation are not known, NPY neurotransmission within the hypothalamus appears to contribute to glucoregulatory feeding. Here we examine the involvement of hindbrain NPY neurons in glucoregulation using in situ hybridization to assess their responsiveness to glucoprivation. The hindbrain NPY innervation of the hypothalamus is derived from cell bodies that coexpress norepinephrine or epinephrine. Therefore, we quantified NPY mRNA hybridization signal in hindbrain catecholamine cell groups 90 min after subcutaneous administration of the glycolytic inhibitor 2-deoxy-d-glucose (2DG, 250 mg/kg) to male rats. Catecholamine cell groups A1, A1/C1 and C2 (that provide the major NPY innervation of the hypothalamus) showed a basal level of NPY mRNA hybridization signal that was dramatically increased by 2DG. In C1 and C3, where basal NPY mRNA expression was close to or below our detection threshold, the hybridization signal was also significantly increased by 2DG. In cell groups A2, A5, A6 and A7, neither basal nor 2DG-stimulated NPY mRNA expression was detected. Hypothalamic microinjection of the retrogradely transported catecholamine immunotoxin saporin conjugated to anti-dopamine-beta-hydroxylase destroyed hindbrain catecholamine/NPY neurons and abolished basal and 2DG-stimulated increases in NPY expression in hindbrain cell groups. The responsiveness of hindbrain NPY neurons to glucose deficit suggests that these neurons participate in glucoprivic feeding or other glucoregulatory responses.