Immunolesion of norepinephrine and epinephrine afferents to medial hypothalamus alters basal and 2-deoxy-D-glucose-induced neuropeptide Y and agouti gene-related protein messenger ribonucleic acid expression in the arcuate nucleus

Endocrinology. 2003 Jan;144(1):75-83. doi: 10.1210/en.2002-220659.

Abstract

Neuropeptide Y (NPY) and agouti gene-related protein (AGRP) are orexigenic peptides of special importance for control of food intake. In situ hybridization studies have shown that NPY and AGRP mRNAs are increased in the arcuate nucleus of the hypothalamus (ARC) by glucoprivation. Other work has shown that glucoprivation stimulates food intake by activation of hindbrain glucoreceptor cells and requires the participation of rostrally projecting norepinephrine (NE) or epinephrine (E) neurons. Here we determine the role of hindbrain catecholamine afferents in glucoprivation-induced increase in ARC NPY and AGRP gene expression. The selective NE/E immunotoxin saporin-conjugated antidopamine-beta-hydroxylase (anti-dbetah) was microinjected into the medial hypothalamus and expression of AGRP and NPY mRNA was analyzed subsequently in the ARC under basal and glucoprivic conditions using (33)P-labeled in situ hybridization. Saporin-conjugated anti-dbetah virtually eliminated dbetah-immunoreactive terminals in the ARC without causing nonspecific damage. These lesions significantly increased basal but eliminated 2-deoxy-D-glucose-induced increases in AGRP and NPY mRNA expression. Results indicate that hindbrain catecholaminergic neurons contribute to basal NPY and AGRP gene expression and mediate the responsiveness of NPY and AGRP neurons to glucose deficit. Our results also suggest that catecholamine neurons couple potent orexigenic neural circuitry within the hypothalamus with hindbrain glucose sensors that monitor brain glucose supply.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Afferent Pathways / physiology*
  • Agouti-Related Protein
  • Animals
  • Antibodies / pharmacology
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Catecholamines / physiology*
  • Deoxyglucose / pharmacology*
  • Dopamine beta-Hydroxylase / immunology
  • Dopamine beta-Hydroxylase / physiology
  • Epinephrine / physiology
  • Gene Expression / drug effects
  • Glucose / deficiency
  • Hypothalamus, Middle / drug effects
  • Hypothalamus, Middle / physiology*
  • Immunohistochemistry
  • Immunotoxins / pharmacology
  • In Situ Hybridization
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Microinjections
  • Neuropeptide Y / genetics*
  • Norepinephrine / physiology
  • Proteins / genetics*
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Agouti-Related Protein
  • Antibodies
  • Catecholamines
  • Immunotoxins
  • Intercellular Signaling Peptides and Proteins
  • Neuropeptide Y
  • Proteins
  • RNA, Messenger
  • Deoxyglucose
  • Dopamine beta-Hydroxylase
  • Glucose
  • Norepinephrine
  • Epinephrine