Affiliation:
1. Division of Neuroscience, Oregon National Primate Research Center and Oregon Health and Science University, Beaverton, OR 97006, USA.
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 (Lep
ob
/Lep
ob
) mice and leptin treatment in adulthood does not reverse these neuroanatomical defects. However, treatment of Lep
ob
/Lep
ob
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.
Publisher
American Association for the Advancement of Science (AAAS)
Cited by
1016 articles.
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