First Author | Fetissov SO | Year | 2005 |
Journal | Eur J Neurosci | Volume | 22 |
Issue | 12 | Pages | 3217-28 |
PubMed ID | 16367788 | Mgi Jnum | J:104309 |
Mgi Id | MGI:3611652 | Doi | 10.1111/j.1460-9568.2005.04513.x |
Citation | Fetissov SO, et al. (2005) Alterations of arcuate nucleus neuropeptidergic development in contactin-deficient mice: comparison with anorexia and food-deprived mice. Eur J Neurosci 22(12):3217-28 |
abstractText | 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. |