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

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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  • Running increases cell survival as well as BDNF levels and phosphorylation of AKT.

    “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

    The Abstract reports that acute running increased hippocampal BDNF mRNA, BDNF protein, and Akt phosphorylation in wild-type mice. It describes increased cellular survival signaling, but does not report a measurement showing that more cells survived. The Results (Phospho-Akt) likewise measure Akt activation, not cell survival; page numbers are unavailable in our copy. (LLM, conf=0.89)

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  • Running or the norepinephrine reuptake inhibitor reboxetine increase the levels of BDNF in a CREB-dependent fashion.

    “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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Research works printed but not linked: 2

  1. Ivy AS Rodriguez FG Garcia C Chen MJ Russo-Neustadt AA 2003 Specific noradrenergic and serotonergic blockade inhibits the activation of hippocampal brain-derived neurotrophic factor expression resulting from physical activity and antidepressant treatment Pharmacology, Biochemistry and Behavior 75 81 88 12759116
  2. Segal RA 2003 Selectivity in neurotrophin signaling: Theme and variations Annual Review of Neuroscience 26 299 330 12598680

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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
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 › 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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