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

Dec 19, 2002Endocrinology

Damage to stress-related nerve inputs to the middle hypothalamus changes normal and sugar-induced signals for hunger-related proteins in the appetite control area

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Abstract

Microinjection of a selective NE/E immunotoxin significantly increased basal AGRP and NPY mRNA expression in the arcuate nucleus of the hypothalamus.

Glucoprivation is associated with increased expression of NPY and AGRP mRNAs in the arcuate nucleus.
Activation of hindbrain glucoreceptor cells is linked to stimulated food intake during glucoprivation.
The loss of dbetah-immunoreactive terminals in the ARC did not cause nonspecific damage.
Hindbrain catecholaminergic neurons likely contribute to basal expression levels of NPY and AGRP.
These neurons may mediate the response of NPY and AGRP to conditions of low glucose.

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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.

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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

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