Intraventricular lactate infusion attenuates the transactivational effects of 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 central compensatory responses to glucose substrate imbalance are initiated by regulatory signals of periventricular origin. Since the glycolytic endproduct, lactate, is a preferred substrate for central neuronal respiration, we investigated whether intracerebroventricular (i.c.v.) infusion of this monocarboxylate fuel attenuates transactivational effects of glucoprivation on PVN and SON AVP neurons. Continuous intraventricular infusion of sodium lactate (1.0 or 10.0 microM/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 injections was processed for colocalization of cytoplasmic AVP- and nuclear Fos-immunoreactivity (Fos-ir). Fos-ir was absent from the PVN and SON of rats treated by i.c.v. infusion of vehicle or either dose of lactate. Intraventricular administration of 10.0 microM lactate/h, but not the lower dose, significantly decreased mean numbers of colabeled AVP neurons in each structure in glucoprivic animals. These data suggest that Fos stimulus-transcription cascade is activated in these cells by decreased central availability of this monocarboxylate fuel, and that cellular sources of regulatory signaling of lactate utilization exist within the periventricular CNS.
Briski
K P
KP
Division of Basic Pharmaceutical Sciences, College of Pharmacy, Northeast Louisiana University, Monroe 71209-0470, USA. pybriski@alpha.nlu.edu
D000818:Animals; D003847:Deoxyglucose / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000172:deficiency; D007276:Injections, Intraventricular; D019344:Lactic Acid / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013495:Supraoptic Nucleus / Q000166:cytology*; D014667:Vasopressins / Q000502:physiology*
D016760:Proto-Oncogene Proteins c-fos; D014667:Vasopressins; D019344:Lactic Acid; D003847:Deoxyglucose; D005947:Glucose