Jokiaho A, Watts AG (2016) Catecholaminergic innervation and the neuronal activation of hypothalamic glucose sensitive regions during rapid- and slow-onset hypoglycemia in adult male rats.. Neuroscience 2016 Abstracts 256.21 / CCC20. Society for Neuroscience, San Diego, CA.
Summary: Hypoglycemic counterregulation is mediated by glucosensors located in the hypothalamus, hindbrain, and portal-mesenteric veins. But which are engaged is rate-dependent, with portal vein sensors being obligatory for slow- but not rapid-onset hypoglycemia. Slow-onset hypoglycemia is particularly prevalent with insulin therapy in type 1 diabetes. We have previously shown that hindbrain-to-hypothalamus catecholaminergic (CA) projections are required for sympathoadrenal responses to slow- but not rapid-onset hypoglycemia, and that rapid- but not slow-onset hypoglycemia significantly increases CA/Fos colocalization in the ventrolateral medulla. These results show that the organization of a hypoglycemia-responsive brain networks is rather complex, and involves a set of what are likely parallel but interactive networks, each of which is responsible for controlling epinephrine, glucagon, and glucocorticoid responses. We now examine how various forebrain cell groups known to be important for glycemic regulation respond to , and how these responses are impacted by removing hindbrain-to-hypothalamus CA projections using injections of the immunotoxin, saporin conjugated to anti-DBH (DSAP) into the hypothalamic paraventricular nucleus (PVH). These injections remove CA inputs to the PVH and other regions within the medial hypothalamus. We then examined whether DSAP lesions affected Fos responses to slow- and rapid-onset insulin-induced hypoglycemia in key forebrain regions. We found that removing CA innervation differentially influences regional hypothalamic Fos responses to slow- and rapid-onset insulin-induced hypoglycemia. Rapid-onset hypoglycemia produced significantly greater Fos activations in the medial and lateral parvocellular and lateral parts of the PVH, parts of the lateral hypothalamus (LHA), the bed nucleus of the stria terminalis that was significantly reduced in all these regions with DSAP lesions. Of particular interest was the altered Fos in LHA regions that contain orexin neurons. We found that 27% of Fos activated neurons colocalized with orexin neurons in rapid-onset hypoglycemia, but this colocalization was significantly reduced by DSAP lesions. Furthermore we used a retrogradely transported polysynaptic neurotropic virus (PRV-152) injected into adrenal gland to show that 25% of PRV-labeled neurons in the LHA colocalized with orexin neurons. These results show that hindbrain-to-hypothalamus CA projections provide hypoglycemia-related information to regions of the forebrain in a rate-dependent way, with orexin neurons playing a particularly prominent role for sympathoadrenal responses.
Related Products: Anti-DBH-SAP (Cat. #IT-03)