Alterations of arcuate nucleus neuropeptidergic development in contactin-deficient mice: comparison with anorexia and food-deprived mice.
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.
Fetissov
Sergueï O
SO
Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden. Serguei.Fetissov@univ-rouen.fr
Bergström
Ulrika
U
Johansen
Jeanette E
JE
Hökfelt
Tomas
T
Schalling
Martin
M
Ranscht
Barbara
B
D054369:Agouti-Related Protein; D000818:Animals; D000855:Anorexia / Q000378:metabolism*; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency* / Q000378:metabolism; D058967:Contactin 1; D058966:Contactins; D005508:Food Deprivation / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D007028:Hypothalamic Hormones / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins; D008543:Melanins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D010907:Pituitary Hormones / Q000235:genetics / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D000521:alpha-MSH / Q000235:genetics / Q000378:metabolism
D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D015816:Cell Adhesion Molecules, Neuronal; C548670:Cntn1 protein, mouse; D058967:Contactin 1; D058966:Contactins; D007028:Hypothalamic Hormones; D036341:Intercellular Signaling Peptides and Proteins; D008543:Melanins; D009478:Neuropeptide Y; D010907:Pituitary Hormones; D011506:Proteins; D012333:RNA, Messenger; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; C019463:melanin-concentrating hormone