Home LiteratureArticle Details
PMID: 15249684 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Essential role of brain-derived neurotrophic factor in adult hippocampal function.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 29 ·2004-07-20 ·Pages 10827-32

Monteggia LM, Barrot M, Powell CM, Berton O, Galanis V, Gemelli T, Meuth S, Nagy A, Greene RW, Nestler EJ

Abstract

Brain-derived neurotrophic factor (BDNF) regulates neuronal development and function. However, it has been difficult to discern its role in the adult brain in influencing complex behavior. Here, we use a recently developed inducible knockout system to show that deleting BDNF in broad forebrain regions of adult mice impairs hippocampal-dependent learning and long-term potentiation. We use the inducible nature of this system to show that the loss of BDNF during earlier stages of development causes hyperactivity and more pronounced hippocampal-dependent learning deficits. We also demonstrate that the loss of forebrain BDNF attenuates the actions of desipramine, an antidepressant, in the forced swim test, suggesting the involvement of BDNF in antidepressant efficacy. These results establish roles for BDNF in the adult, and demonstrate the strength of this inducible knockout system in studying gene function in the adult brain.

MeSH Terms
Animals Antidepressive Agents, Tricyclic/metabolism Brain-Derived Neurotrophic Factor/genetics,metabolism Desipramine/metabolism Electrophysiology Hippocampus/cytology,metabolism In Situ Hybridization Learning/physiology Mice Mice, Knockout Motor Activity/physiology
Chemicals
Antidepressive Agents, Tricyclic Brain-Derived Neurotrophic Factor Desipramine
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Monteggia Lisa M
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9070, USA. lisa.monteggia@utsouthwestern.edu
Barrot Michel
Powell Craig M
Berton Olivier
Galanis Victor
Gemelli Terry
Meuth Sven
Nagy Andreas
Greene Robert W
Nestler Eric J
References (32)
32 references, click to expand
  1. Early restriction of peripheral and proximal cell lineages during formation of the lung.
    Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10482-7 PMID: 12145322
  2. Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine.
    Nature. 1999 Sep 16;401(6750):272-6 PMID: 10499584
  3. Transgenic targeting with regulatory elements of the human CD34 gene.
    Blood. 2002 Dec 15;100(13):4410-9 PMID: 12393582
  4. Trk receptors: roles in neuronal signal transduction.
    Annu Rev Biochem. 2003;72:609-42 PMID: 12676795
  5. The presynaptic active zone protein RIM1alpha is critical for normal learning and memory.
    Neuron. 2004 Apr 8;42(1):143-53 PMID: 15066271
  6. Essential role for TrkB receptors in hippocampus-mediated learning.
    Neuron. 1999 Oct;24(2):401-14 PMID: 10571233
  7. Murine models of depression.
    Psychopharmacology (Berl). 1999 Nov;147(1):14-6 PMID: 10591858
  8. Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities.
    Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15239-44 PMID: 10611369
  9. Cloning and localization of the hyperpolarization-activated cyclic nucleotide-gated channel family in rat brain.
    Brain Res Mol Brain Res. 2000 Sep 30;81(1-2):129-39 PMID: 11000485
  10. Brain-derived neurotrophic factor in the control human brain, and in Alzheimer's disease and Parkinson's disease.
    Prog Neurobiol. 2001 Jan;63(1):71-124 PMID: 11040419
  11. Neurotrophins and activity-dependent plasticity.
    Prog Brain Res. 2000;128:183-91 PMID: 11105678
  12. Behavioral despair in mice: a primary screening test for antidepressants.
    Arch Int Pharmacodyn Ther. 1977 Oct;229(2):327-36 PMID: 596982
  13. Neurotrophins as synaptic modulators.
    Nat Rev Neurosci. 2001 Jan;2(1):24-32 PMID: 11253356
  14. Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity.
    Mol Endocrinol. 2001 Oct;15(10):1748-57 PMID: 11579207
  15. Aggressive behavioral phenotypes in mice.
    Behav Brain Res. 2001 Nov 1;125(1-2):167-81 PMID: 11682108
  16. Postsynaptic Induction of BDNF-Mediated Long-Term Potentiation.
    Science. 2002 Mar 1;295(5560):1729-34 PMID: 11872844
  17. Timing the doxycycline yields different patterns of genomic recombination in brain neurons with a new inducible Cre transgene.
    J Neurosci Res. 2002 Apr 15;68(2):248-53 PMID: 11948670
  18. Cre-stimulated recombination at loxP-containing DNA sequences placed into the mammalian genome.
    Nucleic Acids Res. 1989 Jan 11;17(1):147-61 PMID: 2783482
  19. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters.
    Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5547-51 PMID: 1319065
  20. Mice lacking brain-derived neurotrophic factor develop with sensory deficits.
    Nature. 1994 Mar 10;368(6467):147-50 PMID: 8139657
  21. Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus.
    Science. 1995 Mar 17;267(5204):1658-62 PMID: 7886457
  22. Brain-derived neurotrophic factor rapidly enhances synaptic transmission in hippocampal neurons via postsynaptic tyrosine kinase receptors.
    Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):8074-7 PMID: 7644540
  23. Recombinant BDNF rescues deficits in basal synaptic transmission and hippocampal LTP in BDNF knockout mice.
    Neuron. 1996 Jun;16(6):1137-45 PMID: 8663990
  24. Conditional gene targeting.
    J Clin Invest. 1996 Aug 1;98(3):600-3 PMID: 8698848
  25. Virus-mediated gene transfer into hippocampal CA1 region restores long-term potentiation in brain-derived neurotrophic factor mutant mice.
    Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12547-52 PMID: 8901619
  26. Intact spatial learning and memory in transgenic mice with reduced BDNF.
    Neuroreport. 1997 Feb 10;8(3):779-82 PMID: 9106766
  27. Opposing roles for endogenous BDNF and NT-3 in regulating cortical dendritic growth.
    Neuron. 1997 May;18(5):767-78 PMID: 9182801
  28. A molecular and cellular theory of depression.
    Arch Gen Psychiatry. 1997 Jul;54(7):597-606 PMID: 9236543
  29. Learning deficit in BDNF mutant mice.
    Eur J Neurosci. 1997 Dec;9(12):2581-7 PMID: 9517463
  30. Transgenic animals with inducible, targeted gene expression in brain.
    Mol Pharmacol. 1998 Sep;54(3):495-503 PMID: 9730908
  31. Generalized lacZ expression with the ROSA26 Cre reporter strain.
    Nat Genet. 1999 Jan;21(1):70-1 PMID: 9916792
  32. Neurotrophin-evoked depolarization requires the sodium channel Na(V)1.9.
    Nature. 2002 Oct 17;419(6908):687-93 PMID: 12384689
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.0402141101
Email
lisa.monteggia@utsouthwestern.edu
Published
2004-07-20
Epub
2004-00-12
Pages
10827-32
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC490019
Subset
IM
Grants
NIMH NIH HHS · K08 MH065975-04 · United States
NIMH NIH HHS · K08 MH065975 · United States
NIMH NIH HHS · K08 MH065975-02 · United States
NIMH NIH HHS · K08 MH065975-05 · United States
NIMH NIH HHS · K08 MH065975-01A1 · United States
NIMH NIH HHS · K08 MH065975-03 · United States
External Links
PubMed source DOI: 10.1073/pnas.0402141101 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2