Gender-Specific Impact of Brain-Derived Neurotrophic Factor Signaling on Stress-Induced Depression-Like Behavior
Open accessAbstract
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.
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Conditional knockout of BDNF in the forebrain shows the same sex-specific incongruity in stress-induced depressive-like behavior.
“This conditional knockout of BDNF in the forebrain displayed the same sex-specific incongruity in stress-induced depressive-like behavior (Autry et al. 2009).”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Autry et al. 2009
The Abstract Results report that forebrain BDNF deletion increased susceptibility to some stress-related behaviors in females but not males. However, the Introduction identifies the mice tested under chronic stress as inducible knockouts and distinguishes that line from the authors’ conditional knockout line; the result is not established for that separate line. (LLM, conf=0.82)
Experimental — accuracy not yet measuredRemoval of ovarian hormones in rodents decreases the pro-depressant or anxiogenic effects of stress while simultaneously increasing the negative effects of stress on spatial and non-spatial memory.
“removal of ovarian hormones decreases the pro–depressant or anxiogenic effects of stress, while simultaneously increasing the negative effects of stress on spatial and non–spatial memory85, 91, 92”
From Neurobiology of resilience (2012) · cites this paper as [91]
BDNF is required for the behavioral actions of antidepressants, and deletion increases vulnerability to depression.
“Mutant mouse studies also demonstrate that BDNF is required for the behavioral actions of antidepressants, and that deletion increases vulnerability to depression41,42.”
From Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants (2016) · cites this paper as [41]
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- Authors
- Autry, A. E., Adachi, M., Cheng, P., & Monteggia, L. M.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Monteggia, Lisa M.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 66
- Issue
- 1
- Pages
- 84-90
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2734472
- OpenAlex
- W2094662597
- Cited by
- 154
- References
- 43
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 3 · 2023: 2 · 2022: 9 · 2021: 8 · 2020: 8 · 2019: 11 · 2018: 14 · 2017: 12 · 2016: 12 · 2015: 6 · 2014: 13 · 2013: 11 · 2012: 15
- FWCI
- 9.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (MH 070727, R01MH070727)
- National Institute on Drug Abuse (T32‐DA07290, T32DA007290)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- brain-derived neurotrophic factor, BDNF signaling, depression-like behavior, sex differences, chronic unpredictable mild stress, anxiogenic behavior, anhedonia, estrous cycle, forebrain
- MeSH terms
- Analysis of Variance, Animals, Body Weight, Corticosterone, Depression, Disease Models, Animal, Exploratory Behavior, Female, Food Preferences, Male, Motor Activity, RNA, Messenger, Sex Factors, Stress, Psychological, Sucrose, Signal Transduction, Brain-Derived Neurotrophic Factor, Hindlimb Suspension, Mice
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