Differential responsiveness of dopamine-beta-hydroxylase gene expression to glucoprivation in different catecholamine...

Hindbrain catecholaminergic neurons are key participants in systemic glucoregulation. However, the specific subpopulations critical for glucoregulatory function have not been fully identified. Here we used in situ hybridization and immunohistochemistry to investigate effects of glucoprivation on expression of the gene for the catecholamine biosynthetic enzyme, dopamine-beta-hydroxylase (DBH), to further localize the critical cell populations. Glucoprivation induced by the glycolytic inhibitor, 2-deoxy-D-glucose (2DG) (250 mg/kg) increased total DBH mRNA expression in caudal ventrolateral medullary cell groups (namely A1, the A1/C1 overlap, and the middle portion of C1) from six to 49 times control levels. In retrofacial C1, no enhancement was observed. In the dorsomedial medulla, hybridization signal was modestly increased (tripled) in A2 but was not increased in the area postrema. Previous microinjection of the retrogradely transported catecholamine immunotoxin (anti-DBH-saporin, or DSAP) into the paraventricular nucleus of the hypothalamus reduced the number of DBH-immunoreactive cells in cell groups known to project to the paraventricular nucleus of the hypothalamus as well as reducing the 2DG-stimulated increases in total DBH mRNA expression in the caudal ventrolateral medulla and A2. The strong enhancement of DBH gene expression by glucoprivation is consistent with the demonstrated importance of catecholaminergic neurons for glucoregulation. The differential sensitivity of these neurons to glucoprivation is evidence of functional specialization within the total population. The pattern of 2DG-induced gene expression indicates that the ventrolateral medulla contains the vast majority of catecholamine neurons responsive to glucoprivation.