Anorexigenic melanocortin signaling in the hypothalamus is augmented in association with failure-to-thrive in a transgenic mouse model for Prader-Willi syndrome.
As in Prader-Willi syndrome (PWS) infants, mouse models of PWS display failure-to-thrive during the neonatal period. In rodents, the hypothalamic neuropeptide, Neuropeptide Y (NPY) and Agouti-related peptide (AgrP) stimulate while alpha-melanocyte stimulating hormone (alpha-MSH) inhibits appetite. We hypothesized that altered expression of these neuropeptides in the hypothalamus may underlie the failure-to-thrive in PWS neonatal mice. To test this hypothesis we evaluated mRNA expression of Npy, Agrp, and Pomc by in situ hybridization in the hypothalamic arcuate nucleus (ARC) of 3-day-old female and male PWS neonates. The results showed that Agrp mRNA expression was decreased relative to wild-type (WT) controls in neonates of both sexes, while mRNA expression of Pomc was upregulated in PWS neonates. Since AgrP and the Pomc-derived peptide, alpha-MSH, are functional antagonists at melanocortin 4 receptors in the hypothalamic regulation of appetitive behavior, these results show that robust anorexigenic melanocortin signaling, may contribute to the failure-to-thrive in PWS neonatal mice.
Ge
Yin- Lin
Y
University of Florida McKnight Brain Institute, College of Medicine, Department of Neuroscience, PO Box 100244, Gainesville, FL 32610, USA.
Ohta
Tohru
T
Driscoll
Daniel J
DJ
Nicholls
Robert D
RD
Kalra
Satya P
SP
D054369:Agouti-Related Protein; D000818:Animals; D000831:Animals, Newborn; D000855:Anorexia / Q000378:metabolism*; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D011218:Prader-Willi Syndrome / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D011506:Proteins; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin