title: Brain-derived neurotrophic factor conditional knockouts show gender differences in depression-related behaviors.
abstract: 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.
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9070, USA. lisa.monteggia@utsouthwestern.edu
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Monteggia
authors.forename: Bryan
authors.initials: B
authors.lastname: Luikart
authors.forename: Michel
authors.initials: M
authors.lastname: Barrot
authors.forename: David
authors.initials: D
authors.lastname: Theobold
authors.forename: Irena
authors.initials: I
authors.lastname: Malkovska
authors.forename: Serge
authors.initials: S
authors.lastname: Nef
authors.forename: Luis F
authors.initials: LF
authors.lastname: Parada
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nestler
mesh_terms: D000483:Alleles; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001008:Anxiety Disorders / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003866:Depressive Disorder / Q000235:genetics*; D003891:Desipramine / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D016548:Prosencephalon / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D012737:Sex Factors; D013315:Stress, Psychological / Q000150:complications
chemical_list: D000929:Antidepressive Agents, Tricyclic; D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D003891:Desipramine