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Hindbrain metabolic deficiency regulates ventromedial hypothalamic nucleus glycogen metabolism and glucose‑regulatory signaling

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The catecholamine norepinephrine (NE) links hindbrain metabolic‑sensory neurons with downstream gluco‑regulatory loci, including the ventromedial hypothalamic nucleus (VMN). Exogenous NE up‑regulates VMN expression of glutamate decarboxylase (GAD), biomarker for the gluco‑inhibitory transmitter γ‑aminobutryic acid (GABA). Brain glycogen phosphorylase (GP)‑muscle (GPmm) and ‑brain (GPbb) variants are stimulated in vitro by NE or energy deficiency, respectively. Current research investigated whether lactoprivic‑driven VMN NE signaling regulates GABA and if VMN GPmm and GPbb profiles react differently to that deficit cue. Male rats were pretreated by caudal fourth ventricle delivery of the selective catecholamine neurotoxin 6‑hydroxydopamine (6OHDA) ahead of the monocarboxylate transporter inhibitor alpha‑cyano‑4‑hydroxycinnamic acid (4CIN). Micropunch‑dissected VMN tissue was analyzed by Western blot and ELISA to assess NE‑dependent 4CIN regulation of GAD and GP variant protein expression and NE activity. 4CIN caused 6OHDA‑reversible augmentation of VMN NE content and plasma glucose and counter‑regulatory hormone levels. 6OHDA stimulated basal VMN GAD expression, but prevented 4CIN stimulation of this profile. Neurotoxin inhibited or increased baseline VMN GPmm and GPbb levels, respectively, in non‑4CIN‑injected rats. 6OHDA deterred 4CIN inhibition of GPmm, but did not prevent drug stimulation of GPbb. Results affirm hindbrain lactoprivic regulation of glucostasis. Hindbrain NE exerts opposite effects on VMN GABA transmission during hindbrain lactostasis vs. ‑privation. VMN norepinephrine‑ vs. energy‑sensitive GP variants are subject to dissimilar NE regulation during energy homeostasis, and respond differently to hindbrain lactoprivation.
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  • School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, USA
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