NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates.
Hypothalamic neurons that express neuropeptide Y (NPY) and agouti-related protein (AgRP) are thought to be critical regulators of feeding behavior and body weight. To determine whether NPY/AgRP neurons are essential in mice, we targeted the human diphtheria toxin receptor to the Agrp locus, which allows temporally controlled ablation of NPY/AgRP neurons to occur after an injection of diphtheria toxin. Neonatal ablation of NPY/AgRP neurons had minimal effects on feeding, whereas their ablation in adults caused rapid starvation. These results suggest that network-based compensatory mechanisms can develop after the ablation of NPY/AgRP neurons in neonates but do not readily occur when these neurons become essential in adults.
Luquet
Serge
S
Howard Hughes Medical Institute and Department of Biochemistry, University of Washington, Box 357370, Seattle, WA 98195, USA.
Perez
Francisco A
FA
Hnasko
Thomas S
TS
Palmiter
Richard D
RD
D000375:Aging / Q000502:physiology; D054369:Agouti-Related Protein; D000818:Animals; D000831:Animals, Newborn; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology; D001835:Body Weight / Q000502:physiology; D004167:Diphtheria Toxin; D005247:Feeding Behavior / Q000502:physiology*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics
C515198:AGRP protein, human; D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D004167:Diphtheria Toxin; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D011506:Proteins; D011956:Receptors, Cell Surface