Maturation of the hypothalamic arcuate agouti-related protein system during postnatal development in the mouse.
The hypothalamic arcuate nucleus (Arc) and its neurons expressing agouti-related protein (AgRP) are key components of the forebrain circuitry involved in long-term regulation of energy homeostasis, including conveying leptin signaling to other hypothalamic and extrahypothalamic regions. In the present work, we investigated the postnatal development (P0, P5, P10, P15, and P21) of this system (AgRP transcript and peptide) in the mouse brain using in situ hybridization and immunohistochemistry. At all stages, AgRP mRNA expression was detected exclusively in the Arc. At P0, AgRP mRNA levels were low, and only a few AgRP-immunoreactive fibers were present reaching, rostrally, the bed nucleus of the stria terminalis and, caudally, the dorsal raphe nucleus. During the following period (P5-P21), the levels of AgRP mRNA gradually increased in the Arc along with a parallel increase in the AgRP fiber density in the hypothalamic regions responsible for control of appetite, including the paraventricular nucleus, as well as in extrahypothalamic regions, including locus coeruleus. These data provide evidence that, in the mouse, the maturation of the AgRP Arc system occurs mainly during the first three postnatal weeks. Together with the existing data on the physiology of appetite and body weight, our data suggest that the first three postnatal weeks in the mouse represents a critical period for the formation of brain mechanisms underlying appetite control via peripheral hormones.
Nilsson
Ida
I
Department of Neuroscience B3:4, Karolinska Institutet, Retzius väg 8, 171 77 Stockholm, Sweden.
Johansen
Jeanette E
JE
Schalling
Martin
M
Hökfelt
Tomas
T
Fetissov
Sergueï O
SO
D000375:Aging / Q000502:physiology; D054369:Agouti-Related Protein; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001111:Arcuate Nucleus of Hypothalamus / Q000254:growth & development*; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009478:Neuropeptide Y / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011247:Pregnancy; D011506:Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D016376:Oligonucleotides, Antisense; D011506:Proteins; D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase