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Science 304 (5667): 108-110

Copyright © 2004 by the American Association for the Advancement of Science

Trophic Action of Leptin on Hypothalamic Neurons That Regulate Feeding

Sebastien G. Bouret, Shin J. Draper, Richard B. Simerly*

Abstract: In adult mammals, the adipocyte-derived hormone leptin acts on the brain to reduce food intake by regulating the activity of neurons in the arcuate nucleus of the hypothalamus (ARH). Here, we report that neural projection pathways from the ARH are permanently disrupted in leptin-deficient (Lepob/Lepob) mice and leptin treatment in adulthood does not reverse these neuroanatomical defects. However, treatment of Lepob/Lepob neonates with exogenous leptin rescues the development of ARH projections, and leptin promotes neurite outgrowth from ARH neurons in vitro. These results suggest that leptin plays a neurotrophic role during the development of the hypothalamus and that this activity is restricted to a neonatal critical period that precedes leptin's acute regulation of food intake in adults.

Division of Neuroscience, Oregon National Primate Research Center and Oregon Health and Science University, Beaverton, OR 97006, USA.

* To whom correspondence should be addressed. E-mail: simerlyr{at}ohsu.edu


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