Cited by 129Nerve injury and regenerationTreatment of Major DepressionNeurogenesis and neuroplasticity mechanisms

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Running exercise-induced up-regulation of hippocampal brain-derived neurotrophic factor is CREB-dependent

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Chen, Michael J., Russo‐Neustadt, Amelia A.·2009·Hippocampus

DOI 10.1002/hipo.20579PMC PMC2756465

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Abstract

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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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
DOI: 10.1002/hipo.20579
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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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Running exercise-induced up-regulation of hippocampal brain-derived neurotrophic factor is CREB-dependent

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