PMID- 14622908
OWN - NLM
STAT- MEDLINE
DCOM- 20040217
LR  - 20220321
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 122
IP  - 3
DP  - 2003
TI  - Interplay between brain-derived neurotrophic factor and signal transduction 
      modulators in the regulation of the effects of exercise on synaptic-plasticity.
PG  - 647-57
AB  - This study was designed to identify molecular mechanisms by which exercise 
      affects synaptic-plasticity in the hippocampus, a brain area whose function, 
      learning and memory, depends on this capability. We have focused on the central 
      role that brain-derived neurotrophic factor (BDNF) may play in mediating the 
      effects of exercise on synaptic-plasticity. In fact, this impact of exercise is 
      exemplified by our finding that BDNF regulates the mRNA levels of two end 
      products important for neural function, i.e. cAMP-response-element binding (CREB) 
      protein and synapsin I. CREB and synapsin I have the ability to modify neuronal 
      function by regulating gene-transcription and affecting synaptic transmission, 
      respectively. Furthermore, we show that BDNF is capable of concurrently 
      increasing the mRNA levels of both itself and its tyrosine kinaseB (TrkB) 
      receptor, suggesting that exercise may employ a feedback loop to augment the 
      effects of BDNF on synaptic-plasticity. The use of a novel microbead injection 
      method in our blocking experiments and Taqman reverse transcription polymerase 
      reaction (RT-PCR) for RNA quantification, have enabled us to evaluate the 
      contribution of different pathways to the exercise-induced increases in the mRNA 
      levels of BDNF, TrkB, CREB, and synapsin I. We found that although BDNF mediates 
      exercise-induced hippocampal plasticity, additional molecules, i.e. the 
      N-methyl-D-aspartate receptor, calcium/calmodulin protein kinase II and the 
      mitogen-activated protein kinase cascade, modulate its effects. Since these 
      molecules have a well-described association to BDNF action, our results 
      illustrate a basic mechanism through which exercise may promote 
      synaptic-plasticity in the adult brain.
FAU - Vaynman, S
AU  - Vaynman S
AD  - Department of Physiological Science, UCLA, 621 Charles E. Young Drive, Los 
      Angeles, CA 90095, USA.
FAU - Ying, Z
AU  - Ying Z
FAU - Gomez-Pinilla, F
AU  - Gomez-Pinilla F
LA  - eng
GR  - NS 38978/NS/NINDS NIH HHS/United States
GR  - NS 39522/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Neurotrophin 3)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Synapsins)
RN  - 0 (protein phosphatase inhibitor-2)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Behavior, Animal
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cyclic AMP Response Element-Binding Protein/genetics/metabolism
MH  - Dizocilpine Maleate/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Hippocampus/cytology/drug effects
MH  - Male
MH  - Microspheres
MH  - Models, Biological
MH  - Neuronal Plasticity/drug effects/*physiology
MH  - Neuroprotective Agents/pharmacology
MH  - Neurotrophin 3/genetics/metabolism
MH  - Physical Conditioning, Animal/*physiology
MH  - Proteins/*metabolism
MH  - RNA, Messenger/biosynthesis
MH  - Random Allocation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Signal Transduction/drug effects/genetics/*physiology
MH  - Synapsins/genetics/metabolism
MH  - Time Factors
EDAT- 2003/11/19 05:00
MHDA- 2004/02/18 05:00
CRDT- 2003/11/19 05:00
PHST- 2003/11/19 05:00 [pubmed]
PHST- 2004/02/18 05:00 [medline]
PHST- 2003/11/19 05:00 [entrez]
AID - S0306452203006109 [pii]
AID - 10.1016/j.neuroscience.2003.08.001 [doi]
PST - ppublish
SO  - Neuroscience. 2003;122(3):647-57. doi: 10.1016/j.neuroscience.2003.08.001.