PMID- 16697351
OWN - NLM
STAT- MEDLINE
DCOM- 20070315
LR  - 20220309
IS  - 0006-3223 (Print)
IS  - 0006-3223 (Linking)
VI  - 61
IP  - 2
DP  - 2007 Jan 15
TI  - Brain-derived neurotrophic factor conditional knockouts show gender differences 
      in depression-related behaviors.
PG  - 187-97
AB  - BACKGROUND: Indirect evidence suggests that loss of brain-derived neurotrophic 
      factor (BDNF) from forebrain regions contributes to an individual's vulnerability 
      for depression, whereas upregulation of BDNF in these regions is suggested to 
      mediate the therapeutic effect of antidepressants. METHODS: We have tested this 
      hypothesis by generating two independent lines of conditional BDNF knockout mice 
      in which the BDNF gene is deleted selectively in forebrain. RESULTS: We show that 
      male conditional knockouts exhibit hyperactivity but normal depression-related 
      behaviors. In contrast, female conditional knockouts display normal locomotor 
      activity but a striking increase in depression-like behavior. We also demonstrate 
      that loss of BDNF in both male and female mice attenuates the actions of the 
      antidepressant desipramine in the forced swim test. CONCLUSIONS: These gender 
      differences in depression-related behaviors in BDNF conditional knockout mice 
      provide direct evidence for a role of BDNF in depression. The results also 
      support the view that forebrain BDNF may be essential in mediating antidepressant 
      efficacy.
FAU - Monteggia, Lisa M
AU  - Monteggia LM
AD  - Department of Psychiatry, The University of Texas Southwestern Medical Center, 
      Dallas, TX 75390-9070, USA. lisa.monteggia@utsouthwestern.edu
FAU - Luikart, Bryan
AU  - Luikart B
FAU - Barrot, Michel
AU  - Barrot M
FAU - Theobold, David
AU  - Theobold D
FAU - Malkovska, Irena
AU  - Malkovska I
FAU - Nef, Serge
AU  - Nef S
FAU - Parada, Luis F
AU  - Parada LF
FAU - Nestler, Eric J
AU  - Nestler EJ
LA  - eng
GR  - MH070727/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060512
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Antidepressive Agents, Tricyclic)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - TG537D343B (Desipramine)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - Antidepressive Agents, Tricyclic/pharmacology
MH  - Anxiety Disorders/genetics
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Depressive Disorder/*genetics
MH  - Desipramine/pharmacology
MH  - Female
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Motor Activity/physiology
MH  - Prosencephalon/pathology
MH  - RNA, Messenger/genetics
MH  - Sex Factors
MH  - Stress, Psychological/complications
EDAT- 2006/05/16 09:00
MHDA- 2007/03/16 09:00
CRDT- 2006/05/16 09:00
PHST- 2005/12/02 00:00 [received]
PHST- 2006/03/03 00:00 [revised]
PHST- 2006/03/09 00:00 [accepted]
PHST- 2006/05/16 09:00 [pubmed]
PHST- 2007/03/16 09:00 [medline]
PHST- 2006/05/16 09:00 [entrez]
AID - S0006-3223(06)00397-0 [pii]
AID - 10.1016/j.biopsych.2006.03.021 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2007 Jan 15;61(2):187-97. doi: 10.1016/j.biopsych.2006.03.021. 
      Epub 2006 May 12.