Platelet-derived growth factor-mediated induction of the synaptic plasticity gene Arc/Arg3.1

Fuwang Peng, Honghong Yao, Xuetao Bai, Xuhui Zhu, Benjamin C. Reiner, Michael Beazely, Keiko Funa, Huangui Xiong, Shilpa J Buch

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Platelet-derived growth factor (PDGF) is a pleiotropic protein with critical roles in both developmental as well as pathogenic processes. In the central nervous system specifically, PDGF is critical for neuronal proliferation and differentiation and has also been implicated as a neuroprotective agent. Whether PDGF also plays a role in synaptic plasticity, however, remains poorly understood. In the present study we demonstrated that in the rat hippocampal neurons PDGF regulated the expression of Arc/Arg3.1 gene that has been implicated in both synapse plasticity and long term potentiation. Relevance of these findings was further confirmed in vivo by injecting mice with intracerebral inoculations of PDGF, which resulted in a rapid induction of Arc in the hippocampus of the injected mice. PDGF induced long term potentiation in rat hippocampal slices, which was abolished by PDGFreceptor-tyrosine kinase inhibitor STI-571.Wealso present evidence that PDGF-mediated induction of Arc/Arg3.1 involved activation of the MAPK/ERK (MEK) pathway. Additionally, induction of Arc/Arg3.1 also involved the upstream release of intracellular calcium stores, an effect that could be blocked by thapsigargin but not by EGTA. Pharmacological approach using inhibitors specific for either MAPK/ERK phosphorylation or calcium release demonstrated that the two pathways converged downstream at a common point involving activation of the immediate early gene Egr-1. Chromatin immunoprecipitation assays demonstrated the binding of Egr-1, but not Egr-3, to the Arc promoter. These findings for the first time, thus, suggest an additional role of PDGF, that of induction of Arc.

Original languageEnglish (US)
Pages (from-to)21615-21624
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number28
DOIs
StatePublished - Jul 9 2010

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Neuronal Plasticity
Platelet-Derived Growth Factor
Plasticity
Genes
Long-Term Potentiation
Rats
Chemical activation
Calcium
Phosphorylation
Immediate-Early Genes
Thapsigargin
MAP Kinase Signaling System
Chromatin Immunoprecipitation
Egtazic Acid
Neurology
Neuroprotective Agents
Protein-Tyrosine Kinases
Synapses
Neurons
Chromatin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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Platelet-derived growth factor-mediated induction of the synaptic plasticity gene Arc/Arg3.1. / Peng, Fuwang; Yao, Honghong; Bai, Xuetao; Zhu, Xuhui; Reiner, Benjamin C.; Beazely, Michael; Funa, Keiko; Xiong, Huangui; Buch, Shilpa J.

In: Journal of Biological Chemistry, Vol. 285, No. 28, 09.07.2010, p. 21615-21624.

Research output: Contribution to journalArticle

Peng, Fuwang ; Yao, Honghong ; Bai, Xuetao ; Zhu, Xuhui ; Reiner, Benjamin C. ; Beazely, Michael ; Funa, Keiko ; Xiong, Huangui ; Buch, Shilpa J. / Platelet-derived growth factor-mediated induction of the synaptic plasticity gene Arc/Arg3.1. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 28. pp. 21615-21624.
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