The DOI matches its Crossref record; 112 of the 112 references it cites were found in a registry or an index.
Running exercise-induced up-regulation of hippocampal brain-derived neurotrophic factor is CREB-dependent
Open accessAbstract
The past decade has witnessed burgeoning evidence that antidepressant medications and physical exercise increase the expression of hippocampal brain‐derived neurotrophic factor (BDNF). This phenomenon has gained widespread appeal, because BDNF is one of the first macromolecules observed to play a central role not only in the treatment of mood disorders, but also in neuronal survival‐, growth‐, and plasticity‐related signaling cascades. Thus, it has become critical to understand how BDNF synthesis is regulated. Much evidence exists that changes in BDNF expression result from the activation/phosphorylation of the transcription factor, cAMP‐response‐element binding protein (CREB) following the administration of antidepressant medications. Utilizing a mouse model genetically engineered with an inducible CREB repressor, our current study provides evidence that increases in BDNF expression and cellular survival signaling resulting from physical exercise are also dependent upon activation of this central transcription factor. The transcription and expression of hippocampal BDNF, as well as the activation of Akt, a key survival signaling molecule, were measured following acute exercise, and also following short‐term treatment with the norepinephrine reuptake inhibitor, reboxetine. We found that both interventions led to a marked increase in hippocampal BDNF mRNA, BDNF protein, and Akt phosphorylation (as well as CREB phosphorylation) in wild‐type mice. As expected, activation of the CREB repressor in mutant mice sharply decreased CREB phosphorylation. In addition, all measures noted above remained at baseline levels when mutant mice exercised or received reboxetine. Increases in BDNF and phospho‐Akt were also prevented when mutant mice received a combination of exercise and antidepressant treatment. The results are discussed in the context of what is currently known about BDNF signaling. © 2009 Wiley‐Liss, Inc.
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“Similarly, running increases cell survival as well as BDNF levels and the phosphorylation of AKT, a key gene for cell survival signaling (Chen and Russo-Neustadt, 2009).”
From Depression and adult neurogenesis: Positive effects of the antidepressant fluoxetine and of physical exercise (2018) · cites this paper as Chen and Russo-Neustadt, 2009
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“Similarly, also running or the norepinephrine reuptake inhibitor reboxetine increase the levels of BDNF, in a CREB-dependent fashion (Chen and Russo-Neustadt, 2009).”
From Depression and adult neurogenesis: Positive effects of the antidepressant fluoxetine and of physical exercise (2018) · cites this paper as Chen and Russo-Neustadt, 2009
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Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 316,394
Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor
Brunet, A., Bonni, A., Zigmond, M. J., Lin, M. Z., Juo, P., Hu, L. S., Anderson, M. J., Arden, K. C., Blenis, J., & Greenberg, M. E. (1999) · Cell · doi:10.1016/s0092-8674(00)80595-4 · Cited by 5,594
Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus
van Praag, H., Kempermann, G., & Gage, F. H. (1999) · Nature Neuroscience · doi:10.1038/6368 · Cited by 3,880
The Neuroendocrinology of Stress: A Never Ending Story
Lightman, S. L. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01711.x · Cited by 3,588
THE CATECHOLAMINE HYPOTHESIS OF AFFECTIVE DISORDERS: A REVIEW OF SUPPORTING EVIDENCE
Schildkraut, J. J. (1965) · American Journal of Psychiatry · doi:10.1176/ajp.122.5.509 · Cited by 3,568
A Neurotrophic Model for Stress-Related Mood Disorders
Duman, R. S., & Monteggia, L. M. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.02.013 · Cited by 3,375
CREB: A Stimulus-Induced Transcription Factor Activated by A Diverse Array of Extracellular Signals
Shaywitz, A. J., & Greenberg, M. E. (1999) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.68.1.821 · Cited by 2,133
A molecular and cellular theory of depression
Duman, R. S. (1997) · Archives of General Psychiatry · doi:10.1001/archpsyc.1997.01830190015002 · Cited by 2,129
Exercise enhances learning and hippocampal neurogenesis in aged mice
van Praag, H., Shubert, T., Zhao, C., & Gage, F. H. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1731-05.2005 · Cited by 2,078
Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression
Shirayama, Y., Chen, A. C.-H., Nakagawa, S., Russell, D. S., & Duman, R. S. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-08-03251.2002 · Cited by 1,654
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Martín‐González, C., González‐Arnay, E., Fernández-Rodríguez, C. M., Rodríguez, A. G., & González‐Reimers, E. (2021) · Springer eBooks · doi:10.1007/978-3-030-67928-6_182-1 · Cited by 4
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Loprinzi, P. D., Lovorn, A., Hamilton, E., & Mincarelli, N. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8081200 · Cited by 4
Jiang, H., Zhao, T., He, C., Liu, B., Ai, W., Chen, Y., & Moriyama, H. (2025) · GeroScience · doi:10.1007/s11357-025-01717-3 · Cited by 2
Movahed, A., Aminizadeh, S., Marefati, H., Shahouzehi, B., Najafipour, H., Sheikhshoaei, S., & Hejazi, K. (2025) · Physiology & Behavior · doi:10.1016/j.physbeh.2025.115076 · Cited by 2
Leońska‐Duniec, A. (2026) · Genes · doi:10.3390/genes17040474 · Cited by 2
Alcohol and Brain-Derived Neurotrophic Factor (BDNF)
Martín‐González, C., González‐Arnay, E., Fernández-Rodríguez, C. M., Rodríguez, A. G., & González‐Reimers, E. (2022) · Springer eBooks · doi:10.1007/978-3-030-92392-1_182 · Cited by 2
Chen, M., Sharko, G., Cuellar, E., & Russo-Neustadt, A. (2018) · Journal of Natural & Ayurvedic Medicine · doi:10.23880/jonam-16000113
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Valdes, J. J. (2009) · FIU - Digital Commons (Florida International University) · doi:10.25148/etd.fi09120801 · Cited by 1
Activation of the TrkB Neurotrophin Receptor by Antidepressant Drugs
Antila, H. (2016) · Työväentutkimus Vuosikirja · Cited by 1
The Effects of Exercise on Neuronal Survival
Chen, M. J. (2015) · doi:10.1002/9781118840634.ch23
Self-citationEFFECTS OF EXERCISE TRAINING ON BRAIN BIOENERGETICS: LACTATE AS A KEY MEDIATOR
Lezi, E. (2013) · KU ScholarWorks (University of Kansas)
Raeisi, P., Alaei, H., Babri, S., Sharifi, M. R., Mohaddes, G., Soleymannezhad, E., & Rashidi, B. (2010)
O’Leary, J. D. (2017) · Cork Open Research Archive (University College Cork, Ireland)
Bouchard-Cannon, P. (2018) · TSpace (University of Toronto)
Delancey, D., & Loprinzi, P. D. (2019) · Journal of Cognitive-Behavioral Psychotherapy and Research · doi:10.5455/jcbpr.5542
Church, D. D. (2018) · Journal of International Crisis and Risk Communication Research
Activity-Dependent Induction of Younger Molecular, Cellular and Organism PhenotypesPreprint
Lissek, T. (2022) · Preprints.org · doi:10.20944/preprints202204.0055.v1
Ghaheri, S., Sakhaie, N., Sadegzadeh, F., Abdollahzadeh, M., & Saadati, H. (2021) · SSRN Electronic Journal · doi:10.2139/ssrn.3945462
Khaledi, N., Jeddi, S., Abbasi, S., Eftekharzadeh, M., Khodadadi, H., Namdari, M., & Tuplin, E. W. N. (2023) · SSRN Electronic Journal · doi:10.2139/ssrn.4587227
de Almeida, C. A. S. (2014) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.17.2014.tde-11122024-171246
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Amawi, H. A., Hammad, A. M., Ibrahim, A., Alsbih, N., Hall, F. S., Alasmari, F. F., & Al‐Trad, B. (2025) · Brain Sciences · doi:10.3390/brainsci15010089
Natural synergistic interventions for depression: Voluntary wheel running and flavonoids
Kong, D., Li, D., Duan, Y., Chen, Y., & Li, T. (2026) · Behavioural Brain Research · doi:10.1016/j.bbr.2026.116088
Tang, S., Pedrero‐Chamizo, R., Gesteiro, E., Quesada, C., Ruiz, M. P., & González‐Gross, M. (2026) · Sci · doi:10.3390/sci8040084
Voluntary Exercise and Hippocampal Memory Enhancement: Decoding the Molecular Blueprint
Razazpour, F., Golkar, A., Heidari, M., Seyedi, F., Hedayati‐Moghadam, M., & Baghcheghi, Y. (2026) · Journal of Molecular Neuroscience · doi:10.1007/s12031-026-02577-y
Metadata
- Authors
- Chen, M. J., & Russo‐Neustadt, A. A.
- Affiliations
- California State University Los Angeles (US)
- Corresponding author
- Chen, Michael J.
- ORCID
- Chen, Michael J.
- Venue
- Hippocampus
- Publisher
- Wiley
- Published
- 2009-03-17
- Volume
- 19
- Issue
- 10
- Pages
- 962-972
- ISSN
- 1050-9631 (ISSN-L)
- 1098-1063
- PMC
- PMC2756465
- OpenAlex
- W1994470316
- Cited by
- 129
- References
- 112
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 9 · 2020: 11 · 2019: 5 · 2018: 15 · 2017: 12 · 2016: 5 · 2015: 5 · 2014: 10 · 2013: 6 · 2012: 6
- FWCI
- 3.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hippocampus (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (MH 59776, R01MH059776)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- brain-derived neurotrophic factor, physical activity, CREB, CREB phosphorylation, Akt phosphorylation, reboxetine, antidepressants, norepinephrine reuptake inhibition, neuroplasticity, mood disorders
- MeSH terms
- Reboxetine, Animals, Cell Survival, Hippocampus, Male, Mice, Inbred Strains, Mice, Transgenic, Morpholines, Phosphorylation, Physical Conditioning, Animal, Random Allocation, RNA, Messenger, Running, Up-Regulation, Cyclic AMP Response Element-Binding Protein, Adrenergic Uptake Inhibitors, Brain-Derived Neurotrophic Factor, Proto-Oncogene Proteins c-akt, Mice
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