RGD Reference Report - Folate regulation of axonal regeneration in the rodent central nervous system through DNA methylation. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

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

Authors: Iskandar, BJ  Rizk, E  Meier, B  Hariharan, N  Bottiglieri, T  Finnell, RH  Jarrard, DF  Banerjee, RV  Skene, JH  Nelson, A  Patel, N  Gherasim, C  Simon, K  Cook, TD  Hogan, KJ 
Citation: Iskandar BJ, etal., J Clin Invest. 2010 May;120(5):1603-16. doi: 10.1172/JCI40000. Epub 2010 Apr 26.
RGD ID: 10054082
Pubmed: PMID:20424322   (View Abstract at PubMed)
PMCID: PMC2860927   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI40000   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
DhfrRataxon regeneration involved_inIMP PMID:20424322BHF-UCL 
MtrRataxon regeneration involved_inIMP PMID:20424322BHF-UCL 
MtrRatcellular response to nitric oxide involved_inIDA PMID:20424322BHF-UCL 
DhfrRatfolic acid metabolic process involved_inIDA PMID:20424322BHF-UCL 
MtrRatmethionine biosynthetic process involved_inIDA PMID:20424322BHF-UCL 
MtrRatresponse to axon injury involved_inIDA PMID:20424322BHF-UCL 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
DhfrRatdihydrofolate reductase activity enablesIDA PMID:20424322BHF-UCL 
MtrRatmethionine synthase activity enablesIDA PMID:20424322BHF-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Dhfr  (dihydrofolate reductase)
Mtr  (5-methyltetrahydrofolate-homocysteine methyltransferase)


Additional Information