Neuropeptide Y mRNA and serotonin innervation in the arcuate nucleus of anorexia mutant mice.
The anorexia (anx) mutation causes reduced food intake in preweanling mice, resulting in death from starvation within 3-4 weeks. In wild-type rodents, starvation induces increased neuropeptide Y (NPY) mRNA levels in the arcuate nucleus that promotes compensatory hyperphagia. Despite severely decreased body weight and food intake at 3-weeks age, anx/anx mice do not show elevated NPY mRNA levels in the hypothalamic arcuate nucleus compared to wild-type/heterozygous littermates. The NPY mRNA levels can be upregulated in normal mice at this chronological age, because 24-h food deprivation increased arcuate NPY mRNA in wild-type littermates. The unresponsiveness of NPY expression in the arcuate of anx/anx mice was paralleled by serotonergic hyperinnervation of the arcuate nucleus, comparable to the serotonergic hyperinnervation previously reported in the rest of the anx/anx brain. This result is consistent with the hypothesis that wasting disorders are accompanied by disregulation of NPY mRNA expression in the arcuate nucleus, and suggests that reduced food intake, the primary behavioral phenotype of the anx/anx mouse, may be the result of altered hypothalamic mechanisms that normally regulate feeding.
Jahng
J W
JW
Laboratory of Molecular Neurobiology, Burke Medical Research Institute, Department of Neurology and Neuroscience, White Plains, NY 10605, USA.
Houpt
T A
TA
Kim
S J
SJ
Joh
T H
TH
Son
J H
JH
D000818:Animals; D000855:Anorexia / Q000503:physiopathology*; D001111:Arcuate Nucleus of Hypothalamus / Q000737:chemistry* / Q000166:cytology / Q000502:physiology; D001835:Body Weight; D018076:DNA, Complementary; D004435:Eating / Q000502:physiology; D005183:Failure to Thrive / Q000503:physiopathology; D005260:Female; D005508:Food Deprivation / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009412:Nerve Fibers / Q000737:chemistry; D009478:Neuropeptide Y / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012701:Serotonin / Q000032:analysis*; D014886:Weaning
D018076:DNA, Complementary; D009478:Neuropeptide Y; D012333:RNA, Messenger; D012701:Serotonin