title: Platelet-derived growth factor-mediated induction of the synaptic plasticity gene Arc/Arg3.1.
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 PDGF receptor-tyrosine kinase inhibitor STI-571. We also 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.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska 68198-5880, USA.
authors.forename: Fuwang
authors.initials: F
authors.lastname: Peng
authors.forename: Honghong
authors.initials: H
authors.lastname: Yao
authors.forename: Xuetao
authors.initials: X
authors.lastname: Bai
authors.forename: Xuhui
authors.initials: X
authors.lastname: Zhu
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Reiner
authors.forename: Michael
authors.initials: M
authors.lastname: Beazely
authors.forename: Keiko
authors.initials: K
authors.lastname: Funa
authors.forename: Huangui
authors.initials: H
authors.lastname: Xiong
authors.forename: Shilpa
authors.initials: S
authors.lastname: Buch
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004594:Electrophysiology; D004789:Enzyme Activation; D005260:Female; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003598:Cytoskeletal Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D010982:Platelet-Derived Growth Factor; C092069:activity regulated cytoskeletal-associated protein; D019869:Phosphatidylinositol 3-Kinases; D002118:Calcium
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