Transcriptional activation of nucleus tractus solitarii/area postrema catecholaminergic neurons by pharmacological inhibition of caudal hindbrain monocarboxylate transporter function.

Evidence that intracerebral lactate administration alters electrophysiological sensitivity of metabolic-signaling neurons and hypoglycemic counterregulation suggests that this substrate fuel is a monitored indicator of in central nervous system energy balance. Catecholaminergic (CA) neurons in the caudal hindbrain nucleus tractus solitarii (NTS)/area postrema (AP) complex participate in the origin and/or relay of stimuli that signal deficient glucose provision to the brain. The present studies evaluated the responsiveness of this neurochemical phenotype to lactate insufficiency by investigating the effects of pharmacological inhibition of local monocarboxylate transporter activity on the transcriptional status of these cells. Adult female rats were sacrificed by transcardial perfusion 2 h after infusion of graded doses of the monocarboxylate transporter inhibitor, alpha-cyano-4-hydroxycinnamic acid (4-CIN), or vehicle into the caudal fourth ventricle, and tissue sections through the NTS/AP were processed by dual-label immunofluorescence histochemistry for demonstration of cytoplasmic tyrosine hydroxylase (TH) and the inducible nuclear AP-1 regulatory factor, Fos. While vehicle administration resulted in negligible Fos immunostaining within the NTS, 4-CIN-treated animals exhibited dose-dependent increases in mean numbers of Fos-ir- and TH-/Fos-ir-positive neurons in this structure. These data show that pharmacological suppression of lactate trafficking in the caudal hindbrain elicits the genomic activation of NTS/AP CA neurons. In light of evidence implicating this neurochemical phenotype in signaling of cellular energy imbalance, the current results support the view that diminished uptake and/or catabolism of lactate may underlie CA neuronal activation of neural pathways governing compensatory behavioral and physiological responses to metabolic substrate deficiency. Copyright 2005 S. Karger AG, Basel