PMID- 19294650
OWN - NLM
STAT- MEDLINE
DCOM- 20091214
LR  - 20240312
IS  - 1098-1063 (Electronic)
IS  - 1050-9631 (Print)
IS  - 1050-9631 (Linking)
VI  - 19
IP  - 10
DP  - 2009 Oct
TI  - Running exercise-induced up-regulation of hippocampal brain-derived neurotrophic 
      factor is CREB-dependent.
PG  - 962-72
LID - 10.1002/hipo.20579 [doi]
AB  - 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.
CI  - Copyright 2008 Wiley-Liss, Inc.
FAU - Chen, Michael J
AU  - Chen MJ
AD  - Department of Biological Sciences, California State University, 5151 State 
      University Dr., Los Angeles, CA 90032, USA. mchen@calstatela.edu
FAU - Russo-Neustadt, Amelia A
AU  - Russo-Neustadt AA
LA  - eng
GR  - R01 MH059776/MH/NIMH NIH HHS/United States
GR  - R01 MH059776-11/MH/NIMH NIH HHS/United States
GR  - MH-59776/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Hippocampus
JT  - Hippocampus
JID - 9108167
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Creb1 protein, mouse)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Morpholines)
RN  - 0 (RNA, Messenger)
RN  - 947S0YZ36I (Reboxetine)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Adrenergic Uptake Inhibitors/pharmacology
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cell Survival/physiology
MH  - Cyclic AMP Response Element-Binding Protein/*metabolism
MH  - Hippocampus/drug effects/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Transgenic
MH  - Morpholines/pharmacology
MH  - Phosphorylation
MH  - Physical Conditioning, Animal/*physiology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Messenger/metabolism
MH  - Random Allocation
MH  - Reboxetine
MH  - Running/*physiology
MH  - Up-Regulation/drug effects/physiology
PMC - PMC2756465
MID - NIHMS97143
EDAT- 2009/03/19 09:00
MHDA- 2009/12/16 06:00
PMCR- 2010/10/01
CRDT- 2009/03/19 09:00
PHST- 2009/03/19 09:00 [entrez]
PHST- 2009/03/19 09:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2010/10/01 00:00 [pmc-release]
AID - 10.1002/hipo.20579 [doi]
PST - ppublish
SO  - Hippocampus. 2009 Oct;19(10):962-72. doi: 10.1002/hipo.20579.