eIF4E Phosphorylation Influences BDNF mRNA Translation in Mouse Dorsal Root Ganglion Neurons

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dc.contributor.ORCID0000-0002-6971-6221 (Price, TJ)en_US
dc.contributor.authorMoy, Jamie K.en_US
dc.contributor.authorKhoutorsky, Arkadyen_US
dc.contributor.authorAsiedu, Marina N.en_US
dc.contributor.authorDussor, Gregoryen_US
dc.contributor.authorPrice, Theodore J.en_US
dc.contributor.utdAuthorMoy, Jamie K.en_US
dc.contributor.utdAuthorAsiedu, Marina N.en_US
dc.contributor.utdAuthorDussor, Gregoryen_US
dc.contributor.utdAuthorPrice, Theodore J.en_US
dc.date.accessioned2018-10-22T19:35:32Z
dc.date.available2018-10-22T19:35:32Z
dc.date.created2018-02-06
dc.descriptionIncludes supplementary materialen_US
dc.description.abstractPlasticity in dorsal root ganglion (DRG) neurons that promotes pain requires activity-dependent mRNA translation. Protein synthesis inhibitors block the ability of many pain-promoting molecules to enhance excitability in DRG neurons and attenuate behavioral signs of pain plasticity. In line with this, we have recently shown that phosphorylation of the 5' cap-binding protein, eIF4E, plays a pivotal role in plasticity of DRG nociceptors in models of hyperalgesic priming. However, mRNA targets of eIF4E phosphorylation have not been elucidated in the DRG. Brain-derived neurotrophic factor (BDNF) signaling from nociceptors in the DRG to spinal dorsal horn neurons is an important mediator of hyperalgesic priming. Regulatory mechanisms that promote pain plasticity via controlling BDNF expression that is involved in promoting pain plasticity have not been identified. We show that phosphorylation of eIF4E is paramount for BDNF mRNA translation in the DRG. BDNF mRNA translation is reduced in mice lacking eIF4E phosphorylation (eIF4E^(S209A)) and pro-nociceptive factors fail to increase BDNF protein levels in the DRGs of these mice despite robust upregulation of BDNF-201 mRNA levels. Importantly, bypassing the DRG by giving intrathecal injection of BDNF in eIF4E^(S209A) mice creates a strong hyperalgesic priming response that is normally absent or reduced in these mice. We conclude that eIF4E phosphorylation-mediated translational control of BDNF expression is a key mechanism for nociceptor plasticity leading to hyperalgesic priming.en_US
dc.description.departmentSchool of Behavioral and Brain Sciencesen_US
dc.description.sponsorshipThis work was supported by NIH Grant nos. R01NS065926, R01GM102575, and R01NS098826.en_US
dc.identifier.bibliographicCitationMoy, Jamie K., Arkady Khoutorsky, Marina N. Asiedu, Gregory Dussor, et al. 2018. "eIF4E phosphorylation Influences BDNF mRNA translation in mouse dorsal root ganglion neurons." Frontiers in Cellular Neuroscience 12, doi:10.3389/fncel.2018.00029en_US
dc.identifier.issn1662-5102en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/6221
dc.identifier.volume12en_US
dc.language.isoenen_US
dc.publisherFrontiers Media SAen_US
dc.relation.urihttp://dx.doi.org/10.3389/fncel.2018.00029en_US
dc.rightsCC BY 4.0 (Attribution)en_US
dc.rights©2018 The Authors.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.source.journalFrontiers In Cellular Neuroscienceen_US
dc.subjectNeuralgiaen_US
dc.subjectProtein Synthesis Inhibitorsen_US
dc.subjectNociceptorsen_US
dc.subjectTouchen_US
dc.subjectAllodyniaen_US
dc.subjectMknk1 proteinen_US
dc.subjectCanceren_US
dc.subjectLTP compounden_US
dc.subjectEukaryotic Initiation Factor-4Een_US
dc.subjectPhosphorylationen_US
dc.subjectBrain-Derived Neurotrophic Factoren_US
dc.subjectGanglia, Spinalen_US
dc.subjectPainen_US
dc.subjectHyperalgesiaen_US
dc.subjectNeoplasmsen_US
dc.subjectMiceen_US
dc.subjectRNAen_US
dc.titleeIF4E Phosphorylation Influences BDNF mRNA Translation in Mouse Dorsal Root Ganglion Neuronsen_US
dc.typeTexten_US
dc.type.genrearticleen_US

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