PMID- 19390590
OWN - NLM
STAT- MEDLINE
DCOM- 20090727
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 4
IP  - 4
DP  - 2009
TI  - Short-term striatal gene expression responses to brain-derived neurotrophic 
      factor are dependent on MEK and ERK activation.
PG  - e5292
LID - 10.1371/journal.pone.0005292 [doi]
LID - e5292
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) is believed to be an 
      important regulator of striatal neuron survival, differentiation, and plasticity. 
      Moreover, reduction of BDNF delivery to the striatum has been implicated in the 
      pathophysiology of Huntington's disease. Nevertheless, many essential aspects of 
      BDNF responses in striatal neurons remain to be elucidated. METHODOLOGY/PRINCIPAL 
      FINDINGS: In this study, we assessed the relative contributions of multipartite 
      intracellular signaling pathways to the short-term induction of striatal gene 
      expression by BDNF. To identify genes regulated by BDNF in these GABAergic cells, 
      we first used DNA microarrays to quantify their transcriptomic responses 
      following 3 h of BDNF exposure. The signal transduction pathways underlying gene 
      induction were subsequently dissected using pharmacological agents and 
      quantitative real-time PCR. Gene expression responses to BDNF were abolished by 
      inhibitors of TrkB (K252a) and calcium (chelator BAPTA-AM and transient receptor 
      potential cation channel [TRPC] antagonist SKF-96365). Interestingly, inhibitors 
      of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2) and extracellular 
      signal-regulated kinase ERK also blocked the BDNF-mediated induction of all 
      tested BDNF-responsive genes. In contrast, inhibitors of nitric oxide synthase 
      (NOS), phosphotidylinositol-3-kinase (PI3K), and CAMK exhibited less prevalent, 
      gene-specific effects on BDNF-induced RNA expression. At the nuclear level, the 
      activation of both Elk-1 and CREB showed MEK dependence. Importantly, 
      MEK-dependent activation of transcription was shown to be required for 
      BDNF-induced striatal neurite outgrowth, providing evidence for its contribution 
      to striatal neuron plasticity. CONCLUSIONS: These results show that the MEK/ERK 
      pathway is a major mediator of neuronal plasticity and other important 
      BDNF-dependent striatal functions that are fulfilled through the positive 
      regulation of gene expression.
FAU - Gokce, Ozgun
AU  - Gokce O
AD  - Laboratory of Functional Neurogenomics, Brain Mind Institute, Ecole Polytechnique 
      Federale de Lausanne, Lausanne, Switzerland.
FAU - Runne, Heike
AU  - Runne H
FAU - Kuhn, Alexandre
AU  - Kuhn A
FAU - Luthi-Carter, Ruth
AU  - Luthi-Carter R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090423
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Calcium/metabolism
MH  - Corpus Striatum/*metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - *Gene Expression
MH  - Mitogen-Activated Protein Kinase Kinases/*metabolism
MH  - Neuronal Plasticity
MH  - Neurons/enzymology/*metabolism
MH  - Nitric Oxide Synthase/genetics/metabolism
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Receptor, trkB/metabolism
PMC - PMC2669182
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2009/04/25 09:00
MHDA- 2009/07/28 09:00
PMCR- 2009/04/23
CRDT- 2009/04/25 09:00
PHST- 2009/02/06 00:00 [received]
PHST- 2009/03/26 00:00 [accepted]
PHST- 2009/04/25 09:00 [entrez]
PHST- 2009/04/25 09:00 [pubmed]
PHST- 2009/07/28 09:00 [medline]
PHST- 2009/04/23 00:00 [pmc-release]
AID - 09-PONE-RA-08567R1 [pii]
AID - 10.1371/journal.pone.0005292 [doi]
PST - ppublish
SO  - PLoS One. 2009;4(4):e5292. doi: 10.1371/journal.pone.0005292. Epub 2009 Apr 23.