The DOI matches its Crossref record; 29 of the 31 references it cites were found in a registry or an index.
Resilience to Chronic Stress Is Mediated by Hippocampal Brain-Derived Neurotrophic Factor
Open accessAbstract
Chronic stress is a trigger for several psychiatric disorders, including depression; however, critical individual differences in resilience to both the behavioral and the neurochemical effects of stress have been reported. A prominent mechanism by which the brain reacts to acute and chronic stress is activation of the hypothalamic–pituitary–adrenal (HPA) axis, which is inhibited by the hippocampus via a polysynaptic circuit. Alterations in secretion of stress hormones and levels of brain-derived neurotrophic factor (BDNF) in the hippocampus were implicated in depression and the effects of antidepressant medications. However, the potential role of hippocampal BDNF in behavioral resilience to chronic stress and in the regulation of the HPA axis has not been evaluated. In the present study, Sprague Dawley rats were subjected to 4 weeks of chronic mild stress (CMS) to induce depressive-like behaviors after lentiviral vectors were used to induce localized BDNF overexpression or knockdown in the hippocampus. The behavioral outcome was measured during 3 weeks after the CMS procedure, then plasma samples were taken for measurements of corticosterone levels, and finally hippocampal tissue was taken for BDNF measurements. We found that hippocampal BDNF expression plays a critical role in resilience to chronic stress and that reduction of hippocampal BDNF expression in young, but not adult, rats induces prolonged elevations in corticosterone secretion. The present study describes a mechanism for individual differences in responses to chronic stress and implicates hippocampal BDNF in the development of neural circuits that control adequate stress adaptations.
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“chronic stress leads to the development of depression– or anxiety–like behaviors in only a subset of laboratory animals22–27.”
From Neurobiology of resilience (2012) · cites this paper as [22]
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“With regards to depression, systemic or intra-hippocampal administration of BDNF exerts antidepressant-like effects 153–155, and over-expression of BDNF in the hippocampus leads to resilience to chronic stress 156.”
From Mechanisms of ketamine action as an antidepressant (2018) · cites this paper as [156]
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Cites
Stress and the brain: from adaptation to disease
de Kloet, E. R., Joëls, M., & Holsboer, F. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1683 · Cited by 4,621
Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse
McGowan, P. O., Sasaki, A., D'Alessio, A. C., Dymov, S., Labonté, B., Szyf, M., Turecki, G., & Meaney, M. J. (2009) · Nature Neuroscience · doi:10.1038/nn.2270 · Cited by 3,531
The concept of allostasis in biology and biomedicine
McEwen, B. S., & Wingfield, J. C. (2003) · Hormones and Behavior · doi:10.1016/s0018-506x(02)00024-7 · Cited by 3,302 · cited 2×
“Association between allostatic overload in young animals and dDG BDNF expression McEwen and Wingfield (2003) have suggested previously that continued social conflict or other environmental changes or stressors drive allostasis (maintaining stability) by prolonged alterations in secretion of CORT,…”
BackgroundNestler, E. J., Barrot, M., DiLeone, R. J., Eisch, A. J., Gold, S. J., & Monteggia, L. M. (2002) · Neuron · doi:10.1016/s0896-6273(02)00653-0 · Cited by 3,217
Causal Relationship Between Stressful Life Events and the Onset of Major Depression
Kendler, K. S., Karkowski, L. M., & Prescott, C. A. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.6.837 · Cited by 2,566 · cited 1×
“Stressful life events are associated with the onset of psychiatric disorders, including major depression (Kendler et al., 1999).”
BackgroundKrishnan, V., Han, M.-H., Graham, D. L., Berton, O., Renthal, W., Russo, S. J., LaPlant, Q., Graham, A., Lutter, M., Lagace, D. C., et al. (2007) · Cell · doi:10.1016/j.cell.2007.09.018 · Cited by 2,307 · cited 4×
“Krishnan et al. (2007) found that brain-derived neurotrophic factor (BDNF) expression in the ventral tegmental area–nucleus accumbens (VTA– NAc) pathway plays a critical role in such resilience and that BDNF knockdown (KD) within the VTA ameliorates depressing effects of social defeat (Krishnan et…”
BackgroundResultInfluentialThe mesolimbic dopamine reward circuit in depression
Nestler, E. J., & Carlezon, W. A. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.09.018 · Cited by 2,059
The link between childhood trauma and depression: insights from HPA axis studies in humans
Heim, C., Newport, D. J., Mletzko, T., Miller, A. H., & Nemeroff, C. B. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.03.008 · Cited by 1,704
Charney, D. S. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.2.195 · Cited by 1,605
Smith, M., Makino, S., Květňanský, R., & Post, R. M. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-03-01768.1995 · Cited by 1,449
Cited by
Sorted by citations
Russo, S. J., Murrough, J. W., Han, M.-H., Charney, D. S., & Nestler, E. J. (2012) · Nature Neuroscience · doi:10.1038/nn.3234 · Cited by 1,206
Mechanisms of ketamine action as an antidepressant
Zanos, P., & Gould, T. D. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.255 · Cited by 1,127
The chronic mild stress (CMS) model of depression: History, evaluation and usage
Willner, P. (2017) · Neurobiology of Stress · doi:10.1016/j.ynstr.2016.08.002 · Cited by 959
Wu, G., Feder, A., Cohen, H., Kim, J. J., Calderon, S., Charney, D. S., & Mathé, A. A. (2013) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2013.00010 · Cited by 887
Intermittent metabolic switching, neuroplasticity and brain health
Mattson, M. P., Moehl, K., Ghena, N., Schmaedick, M., & Cheng, A. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.156 · Cited by 624
Metadata
- Authors
- Taliaz, D., Loya, A., Gersner, R., Haramati, S., Chen, A., & Zangen, A.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Zangen, Abraham
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-03-23
- Volume
- 31
- Issue
- 12
- Pages
- 4475-4483
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6622886
- OpenAlex
- W1965232611
- Cited by
- 311
- References
- 31
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 12 · 2023: 32 · 2022: 21 · 2021: 20 · 2020: 16 · 2019: 27 · 2018: 21 · 2017: 21 · 2016: 17 · 2015: 29 · 2014: 19 · 2013: 20 · 2012: 22
- FWCI
- 8.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Israel Science Foundation (1486/10)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Resilience and Mental Health
- Keywords
- chronic stress, resilience, hippocampus, brain-derived neurotrophic factor, chronic mild stress, depression, hypothalamic-pituitary-adrenal axis, corticosterone, BDNF overexpression, individual differences, stress adaptation, lentiviral vectors
- MeSH terms
- Aging, Animals, Chronic Disease, Corticosterone, Environment, Enzyme-Linked Immunosorbent Assay, Exploratory Behavior, Hippocampus, Hydrocortisone, Hypothalamo-Hypophyseal System, Locomotion, Male, Microinjections, Molecular Sequence Data, Pituitary-Adrenal System, Stress, Psychological, Swimming, Rats, Sprague-Dawley, Brain-Derived Neurotrophic Factor, Reverse Transcriptase Polymerase Chain Reaction, Rats, Resilience, Psychological, Gene Knockdown Techniques
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