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PMID: 10611369 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 26 ·1999-12-21 ·Pages 15239-44

Lyons WE, Mamounas LA, Ricaurte GA, Coppola V, Reid SW, Bora SH, Wihler C, Koliatsos VE, Tessarollo L

Abstract

Brain-derived neurotrophic factor (BDNF) has trophic effects on serotonergic (5-HT) neurons in the central nervous system. However, the role of endogenous BDNF in the development and function of these neurons has not been established in vivo because of the early postnatal lethality of BDNF null mice. In the present study, we use heterozygous BDNF(+/-) mice that have a normal life span and show that these animals develop enhanced intermale aggressiveness and hyperphagia accompanied by significant weight gain in early adulthood; these behavioral abnormalities are known to correlate with 5-HT dysfunction. Forebrain 5-HT levels and fiber density in BDNF(+/-) mice are normal at an early age but undergo premature age-associated decrements. However, young adult BDNF(+/-) mice show a blunted c-fos induction by the specific serotonin releaser-uptake inhibitor dexfenfluramine and alterations in the expression of several 5-HT receptors in the cortex, hippocampus, and hypothalamus. The heightened aggressiveness can be ameliorated by the selective serotonin reuptake inhibitor fluoxetine. Our results indicate that endogenous BDNF is critical for the normal development and function of central 5-HT neurons and for the elaboration of behaviors that depend on these nerve cells. Therefore, BDNF(+/-) mice may provide a useful model to study human psychiatric disorders attributed to dysfunction of serotonergic neurons.

MeSH Terms
Aggression Animals Behavior, Animal Brain/physiopathology Brain-Derived Neurotrophic Factor/deficiency,genetics Dexfenfluramine/pharmacology Female Heterozygote Hyperphagia Male Mice Mice, Mutant Strains Proto-Oncogene Proteins c-fos/biosynthesis Serotonin/metabolism
Chemicals
Brain-Derived Neurotrophic Factor Proto-Oncogene Proteins c-fos Serotonin Dexfenfluramine
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Lyons W E
Neural Development Group, Advanced BioScience Laboratories/Basic Research Program, National Cancer Institute/Frederick Cancer Research and Development Center, Frederick, MD 21702, USA.
Mamounas L A
Ricaurte G A
Coppola V
Reid S W
Bora S H
Wihler C
Koliatsos V E
Tessarollo L
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.26.15239
Published
1999-12-21
Pages
15239-44
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC24804
Subset
IM
Grants
NIMH NIH HHS · F32 MH085433 · United States
NINDS NIH HHS · F32 NS010580 · United States
NINDS NIH HHS · NS 10580 · United States
NIMH NIH HHS · R29MH85433 · United States
External Links
PubMed source DOI: 10.1073/pnas.96.26.15239 PMC Full Text View journal details
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