Gender-specific impact of brain-derived neurotrophic factor signaling on stress-induced depression-like behavior.
BACKGROUND
Major depressive disorder is a leading debilitating disease known to occur at a two-fold higher rate in women than in men. The neurotrophic hypothesis of depression suggests that loss of brain-derived neurotrophic factor (BDNF) may increase susceptibility for depression-like behavior, although direct evidence is lacking.


METHODS
Using the chronic unpredictable stress (CUS) paradigm, we investigated whether male and female mice with inducible BDNF deletion in the forebrain were more susceptible to depression-related behavior.


RESULTS
We demonstrate that in certain behavioral measures the loss of BDNF lowers the threshold for female mice studied at random throughout estrus to display anxiogenic and anhedonic behaviors after chronic stress compared with wild-type female mice. However, the loss of BDNF in forebrain does not increase the susceptibility to depression-like behavior in male mice.


CONCLUSIONS
These gender differences suggest a role for BDNF in mediating some aspects of depression-related behavior in females.
Autry
Anita E
AE
Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA.
Adachi
Megumi
M
Cheng
Pengfei
P
Monteggia
Lisa M
LM
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D003345:Corticosterone / Q000378:metabolism; D003863:Depression / Q000209:etiology*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D005518:Food Preferences; D019417:Hindlimb Suspension / Q000379:methods; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D012737:Sex Factors; D015398:Signal Transduction / Q000502:physiology*; D013315:Stress, Psychological / Q000150:complications*; D013395:Sucrose / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D013395:Sucrose; D003345:Corticosterone