Abstract
Brain-derived neurotrophic factor (BDNF) was studied initially for its role in sensory neuron development. Ablation of this gene in mice leads to death shortly after birth, and abnormalities have been found in both the peripheral and central nervous systems. BDNF and its tyrosine kinase receptor, TrkB, are expressed in hypothalamic nuclei associated with satiety and locomotor activity. In heterozygous mice, BDNF gene expression is reduced and we find that all heterozygous mice exhibit abnormalities in eating behavior or locomotor activity. We also observe this phenotype in independently derived inbred and hybrid BDNF mutant strains. Infusion with BDNF or NT4/5 can transiently reverse the eating behavior and obesity. Thus, we identify a novel non-neurotrophic function for neurotrophins and indicate a role in behavior that is remarkably sensitive to alterations in BDNF activity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adipocytes / cytology
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Animals
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Appetite / genetics
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Appetite / physiology
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Body Weight / drug effects
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Brain-Derived Neurotrophic Factor / blood
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Brain-Derived Neurotrophic Factor / deficiency
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Brain-Derived Neurotrophic Factor / genetics
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Brain-Derived Neurotrophic Factor / physiology*
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Carrier Proteins / analysis
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Feeding Behavior / physiology*
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Female
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Heterozygote
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Humans
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Hypothalamus / cytology
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Hypothalamus / metabolism
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Insulin / blood
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Leptin / blood
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Male
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Mice
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Mice, Inbred Strains
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Mice, Knockout
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Motor Activity / genetics
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Motor Activity / physiology*
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Nerve Tissue Proteins / analysis
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Nerve Tissue Proteins / genetics
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Neuropeptide Y / analysis
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Obesity / genetics
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Obesity / pathology
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RNA, Messenger / analysis
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RNA, Messenger / genetics
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Receptor, trkB / genetics
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Receptors, Cell Surface*
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Receptors, Leptin
Substances
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Brain-Derived Neurotrophic Factor
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Carrier Proteins
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Insulin
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Leptin
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Nerve Tissue Proteins
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Neuropeptide Y
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RNA, Messenger
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Receptors, Cell Surface
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Receptors, Leptin
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cocaine- and amphetamine-regulated transcript protein
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Receptor, trkB