The Journal of Neuroscience, July 15, 1999, 19(14):6111-6121
Distinct Patterns of Neuropeptide Gene Expression in the Lateral
Hypothalamic Area and Arcuate Nucleus Are Associated with
Dehydration-Induced Anorexia
Alan G.
Watts,
Graciela
Sanchez-Watts, and
Andrea B.
Kelly
The Neuroscience Program and the Department of Biological Sciences,
University of Southern California, Los Angeles, California
90089-2520
We have investigated the hormonal and hypothalamic neuropeptidergic
substrates of dehydration-associated anorexia. In situ hybridization and hormone analyses of anorexic and paired
food-restricted rats revealed two distinct profiles. First, both groups
had the characteristic gene expression and endocrine signatures usually associated with starvation: increased neuropeptide Y and decreased proopiomelanocortin and neurotensin mRNAs in the arcuate nucleus (ARH);
increased circulating glucocorticoid but reduced leptin and insulin.
Dehydrated animals are strongly anorexic despite these attributes,
showing that the output of leptin- and insulin-sensitive ARH neurons
that ordinarily stimulate eating must be inhibited. The second pattern
occurred only in anorexic animals and had two components: (1) reduced
corticotropin-releasing hormone (CRH) mRNA in the neuroendocrine
paraventricular nucleus (PVH) and (2) increased CRH and neurotensin
mRNAs in the lateral hypothalamic (LHA) and retrochiasmatic areas.
However, neither corticosterone nor suppressed PVH CRH gene expression
is required for anorexia after dehydration because PVH CRH mRNA in
dehydrated adrenalectomized animals is unchanged from euhydrated
adrenalectomized controls. We also showed that LHA CRH mRNA was
strongly correlated with the intensity of anorexia, increased LHA CRH
gene expression preceded the onset of anorexia, and dehydrated
adrenalectomized animals (which also develop anorexia) had elevated LHA
CRH gene expression with a distribution pattern similar to intact
animals. Finally, we identified specific efferents from the
CRH-containing region of the LHA to the PVH, thereby providing a
neuroanatomical framework for the integration by the PVH of
neuropeptidergic signals from the ARH and the LHA. Together, these
observations suggest that CRH and neurotensin neurons in the LHA
constitute a novel anatomical substrate for their well known anorexic effects.
Key words:
feeding behavior; anorexia; neuropeptides; corticotropin-releasing hormone; arcuate nucleus; lateral hypothalamus; paraventricular nucleus; leptin; glucocorticoid
Copyright © 1999 Society for Neuroscience 0270-6474/99/19146111-11$05.00/0
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