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Running exercise‐induced up‐regulation of hippocampal brain‐derived neurotrophic factor is CREB‐dependent
Author(s) -
Chen Michael J.,
RussoNeustadt Amelia A.
Publication year - 2009
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.20579
Subject(s) - creb , reboxetine , neurotrophic factors , brain derived neurotrophic factor , transcription factor , protein kinase b , hippocampal formation , phosphorylation , neuroscience , endocrinology , tropomyosin receptor kinase b , medicine , chemistry , antidepressant , psychology , hippocampus , microbiology and biotechnology , biology , receptor , reuptake inhibitor , biochemistry , gene
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.