Effects of Intraventricular Corticosterone on Brain cFOS Activation and Hormone Response to Hypoglycemia
Results from the Diabetes Control and Complications Trial have shown that the severity, number of incidents and the time of onset of blindness, kidney failure, and cardiovascular disease, caused by chronic hyperglycemia (high blood sugar), are decreased significantly when insulin is administered to diabetics more frequently. But the more frequently insulin is administered, the more severe and frequent are the patient's bouts of hypoglycemia or low blood sugar. Repeated hypoglycemia then disables the body and the brain's ability to both identify and respond to low blood sugar, leading to metabolic, mental, and psychological dysfunction, and in severe cases coma and death. The question that arises then is which regions of the brain take part in recognizing and restablizing blood sugar levels. To address this question the lab will use immunocytochemical measurement of a protein involved in gene translation initiation, called cFOS, that is produced in the brain in response to numerous types of stimuli including laboratory-induced hypoglycemia. This will then show which parts of the brain are active in recognizing and counteracting hypoglycemia. It has been proposed that the hormone glucocorticoid (CORT) is responsible for the impaired counterregulation that occurs with repeat hypoglycemia. To evaluate this, the lab will treat rats with CORT on the first day and induce hypoglycemia on the second day. This model is then compared to a model with repeat hypoglycemia induced for two successive days. If CORT does disable the brain's counterregulatory responses to repeated hypoglycemia then both models will have similar brain patterns of cFOS activation shown both by the FOS immunoreactivity and by similar levels of hormone responses to hypoglycemia. The lab has suggested that the paraventricular nucleus of the hypothalamus, near the base of the brain, will play a major role in responding to hypoglycemia and thus will have significant patterns of cFOS reactivity. Understanding some of the brain's mechanism which underlie the development of the impaired counterregulatory response may point the way to therapeutic interventions that can by used in insulin-requiring diabetics to maintain normal counterregulatory responses to drops in blood sugar.
