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Folate regulation of axonal regeneration in the rodent central nervous system through DNA methylation.

dc.contributor.author Iskandar, Bermans J
dc.contributor.author Rizk, Elias
dc.contributor.author Meier, Brenton
dc.contributor.author Hariharan, Nithya
dc.contributor.author Bottiglieri, Teodoro
dc.contributor.author Finnell, Richard H
dc.contributor.author Jarrard, David F
dc.contributor.author Banerjee, Ruma V
dc.contributor.author Skene, JH Pate
dc.contributor.author Nelson, Aaron
dc.contributor.author Patel, Nirav
dc.contributor.author Gherasim, Carmen
dc.contributor.author Simon, Kathleen
dc.contributor.author Cook, Thomas D
dc.contributor.author Hogan, Kirk J
dc.coverage.spatial United States
dc.date.accessioned 2011-06-21T17:27:54Z
dc.date.issued 2010-05
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/20424322
dc.identifier 40000
dc.identifier.uri https://hdl.handle.net/10161/4324
dc.description.abstract The folate pathway plays a crucial role in the regeneration and repair of the adult CNS after injury. Here, we have shown in rodents that such repair occurs at least in part through DNA methylation. In animals with combined spinal cord and sciatic nerve injury, folate-mediated CNS axon regeneration was found to depend on injury-related induction of the high-affinity folate receptor 1 (Folr1). The activity of folate was dependent on its activation by the enzyme dihydrofolate reductase (Dhfr) and a functional methylation cycle. The effect of folate on the regeneration of afferent spinal neurons was biphasic and dose dependent and correlated closely over its dose range with global and gene-specific DNA methylation and with expression of both the folate receptor Folr1 and the de novo DNA methyltransferases. These data implicate an epigenetic mechanism in CNS repair. Folic acid and possibly other nontoxic dietary methyl donors may therefore be useful in clinical interventions to promote brain and spinal cord healing. If indeed the benefit of folate is mediated by epigenetic mechanisms that promote endogenous axonal regeneration, this provides possible avenues for new pharmacologic approaches to treating CNS injuries.
dc.language eng
dc.language.iso en_US
dc.publisher American Society for Clinical Investigation
dc.relation.ispartof J Clin Invest
dc.relation.isversionof 10.1172/JCI40000
dc.subject Animals
dc.subject Axons
dc.subject Brain
dc.subject Central Nervous System
dc.subject DNA Methylation
dc.subject DNA Modification Methylases
dc.subject Folic Acid
dc.subject Humans
dc.subject In Situ Hybridization
dc.subject Male
dc.subject Mice
dc.subject Models, Biological
dc.subject Nerve Regeneration
dc.subject Rats
dc.subject Rats, Sprague-Dawley
dc.subject Spinal Cord
dc.subject Tetrahydrofolate Dehydrogenase
dc.title Folate regulation of axonal regeneration in the rodent central nervous system through DNA methylation.
dc.title.alternative
dc.type Journal article
duke.contributor.id Skene, JH Pate|0111966
dc.description.version Version of Record
duke.date.pubdate 2010-5-10
duke.description.issue 5
duke.description.volume 120
dc.relation.journal Journal of Clinical Investigation
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/20424322
pubs.begin-page 1603
pubs.end-page 1616
pubs.issue 5
pubs.organisational-group Basic Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Institute for Brain Sciences
pubs.organisational-group Duke Science & Society
pubs.organisational-group Initiatives
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Neurobiology
pubs.organisational-group School of Medicine
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published
pubs.volume 120
dc.identifier.eissn 1558-8238


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