Jokiaho A, Donovan C, Watts A (2012) Catecholaminergic neurons in the ventrolateral medulla are differentially activated by the rate of fall in blood glucose during hypoglycemia, and are required for the rate-dependent hypoglycemic activation of sympathoadrenal responses. Neuroscience 2012 Abstracts 93.05. Society for Neuroscience, New Orleans, LA.
Summary: Hypoglycemic counterregulation is mediated by glucosensors located in the hypothalamus, hindbrain, and portal-mesenteric veins (PV). We have previously shown that when hypoglycemia develops slowly PV glucose sensing is critical for both the sympathoadrenal response and hindbrain Fos activation. Hindbrain catecholaminergic (CA) neurons provide extensive inputs to the hypothalamus and are key participants in the control of energy homeostasis and in the responses to glycemic challenges. However, the role of the various CA cell groups together with the organization of the circuitry between peripheral and central glucose sensing units and the effectors that mediate counterregulatory response to hypoglycemia are unknown. To investigate the role of CA neurons in this network we use hyperinsulinemic-hypoglycemic clamps to induce fast (20mins)- or slow (75min)-onset hypoglycemia in male Wistar rats with saporin/anti-dopamine β-hydroxylase (DBH) DSAP immunotoxin lesions. The hypothalamic paraventricular nucleus (PVH) was injected bilaterally with DSAP or saporin conjugated to mouse IgG (SAP) as controls. PVH DSAP lesions remove about 80% of the DBH-ir and PNMT-ir cell bodies in the ventrolateral medulla. We found that hypothalamic CA afferents are required for sympathoadrenal (epinephrine and nor-epinephrine) responses to slow- but not fast-onset hypoglycemia. We also found robust Fos activation in CA neurons in the ventrolateral (A1, C1) and the dorsomedial medulla, particularly in the nucleus of the solitary tract (NTS; A2, C2). In rats with intact forebrain CA innervations, fast-onset hypoglycemia led to significantly greater DBH/Fos colocalization in the A1, A1/C1 and C1 regions compared to slow-onset hypoglycemia. We further identified substantial numbers of Fos-positive nuclei colocalized in adrenergic neurons (phenylethanolamine-N-methyltransferase (PNMT)) in the A1/C1 and C1 regions, and again these numbers were greater in fast-onset compared to slow-onset hypoglycemia. In SAP and DSAP animals, slow- and fast -onset hypoglycemia led to robust Fos expression in the area postrema and medial parts of the NTS. However, in these two regions there was virtually no Fos and DBH/PNMT-ir colocalization showing that AP and NTS neurons activated following hypoglycemia are not CA. The mechanisms that process the sensory information responsible for sympathoadrenal counterregulatory responses to fast- and slow-onset hypoglycemia are clearly different. We now show that different rates of hypoglycemia onset engage distinct CA cell groups, which in turn differentially participate in rate-dependent counterregulatory responses.
Related Products: Anti-DBH-SAP (Cat. #IT-03)