16367788

pubmed:Citation

12

A mutation in the Contactin-1 gene results in an ataxic and anorectic phenotype that is apparent by postnatal day 10 and lethal by postnatal day 19 [Berglund et al. (1999) Neuron 24, 739-750]. The resemblance of this phenotype with the anorexia (anx/anx) mouse mutation prompted us to investigate the hypothalamic neurochemistry of Contactin knock-out (KO) mice. Contactin was expressed in the hypothalamic neuropil of wild-type (WT) but not Contactin KO mice. In the KO condition, neuropeptide Y (NPY) and agouti-related protein (AgRP) immunoreactivity (IR) accumulated in the somata of arcuate nucleus neurons, whereas IR for these neuropeptides as well as for alpha-melanocyte-stimulating hormone (alpha-MSH) decreased in the corresponding axon projections. These changes in the pattern of neuropeptide expression in the Contactin-deficient hypothalamus were similar but more pronounced than those found in anx/anx mice. Increased levels of NPY and AgRP and decreased concentrations of pro-opiomelanocortin mRNA in arcuate neurons accompanied these changes. In relating these alterations a 24-h food deprivation period, we observed in 3-week-old WT mice an elevation of NPY- and AgRP-IR in the perikarya of arcuate neurons without notable reduction of NPY- or AgRP-IR in nerve fibers, suggesting that the decrease of arcuate projections can be associated with postnatal anorectic phenotype. Our data implicate Contactin in the postnatal development of the NPY/AgRP and alpha-MSH arcuate neurons and suggest that similar to anx/anx mutant mice, compromised orexigenic signaling via NPY/AgRP neurons may contribute to reduced food intake by the Contactin-mutant animals.

eng

IM

MEDLINE

0953-816X

Print

NLM

3217-28

pubmed-meshheading:16367788-Agouti-Related Protein, pubmed-meshheading:16367788-Animals, pubmed-meshheading:16367788-Anorexia, pubmed-meshheading:16367788-Arcuate Nucleus, pubmed-meshheading:16367788-Cell Adhesion Molecules, Neuronal, pubmed-meshheading:16367788-Contactin 1, pubmed-meshheading:16367788-Contactins, pubmed-meshheading:16367788-Food Deprivation, pubmed-meshheading:16367788-Gene Expression Regulation, pubmed-meshheading:16367788-Hypothalamic Hormones, pubmed-meshheading:16367788-Immunohistochemistry, pubmed-meshheading:16367788-In Situ Hybridization, pubmed-meshheading:16367788-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:16367788-Melanins, pubmed-meshheading:16367788-Mice, pubmed-meshheading:16367788-Mice, Knockout, pubmed-meshheading:16367788-Neuropeptide Y, pubmed-meshheading:16367788-Pituitary Hormones, pubmed-meshheading:16367788-Pro-Opiomelanocortin, pubmed-meshheading:16367788-Proteins, pubmed-meshheading:16367788-RNA, Messenger, pubmed-meshheading:16367788-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16367788-alpha-MSH

Alterations of arcuate nucleus neuropeptidergic development in contactin-deficient mice: comparison with anorexia and food-deprived mice.

Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural