Intraventricular lactate infusion attenuates the transactivational effectsof the glucose antimetabolite, 2-deoxy-D-glucose, on hypothalamic vasopressinergic neurons

Glucopenia stimulates neurohypophyseal arginine vasopressin (AVP) secretion and expression of the transcription factor, Fos, by paraventricular (PVN) and supraoptic (SON) magnocellular neurons. Recent studies suggest that cen tral compensatory responses to glucose substrate imbalance are initiated by regulatory signals of periventricular origin. Since the glycolytic endprod uct, lactate, is a preferred substrate for central neuronal respiration, we investigated whether intracerebroventricular (i.c.v.) infusion of this mon ocarboxylate fuel attenuates transactivational effects of glucoprivation on PVN and SON AVP neurons. Continuous intraventricular infusion of sodium la ctate (1.0 or 10.0 mu M/h) or vehicle was initiated before intraperitoneal (i.p.) injection of the glucose antimetabolite, 2-deoxy-D-glucose (2DG), or saline. Anterior hypothalamic tissue obtained 2 h after systemic injection s was processed for colocalization of cytoplasmic AVP- and nuclear Fos-immu noreactivity (Fos-ir). Fos-ir was absent from the PVN and SON of rats treat ed by i.c.v. infusion of vehicle or either dose of lactate. Intraventricula r administration of 10.0 mu M lactate/h, but not the lower dose, significan tly decreased mean numbers of colabeled AVP neurons in each structure in gl ucoprivic animals. These data suggest that Fos stimulus-transcription casca de is activated in these cells by decreased central availability of this mo nocarboxylate fuel, and that cellular sources of regulatory signaling of la ctate utilization exist within the periventricular CNS. (C) 1999 Elsevier S cience B.V. All rights reserved.