title: Methionine increases BDNF DNA methylation and improves memory in epilepsy.
abstract: OBJECTIVE
  Temporal lobe epilepsy (TLE) patients exhibit signs of memory impairments even when seizures are pharmacologically controlled. Surprisingly, the underlying molecular mechanisms involved in TLE-associated memory impairments remain elusive. Memory consolidation requires epigenetic transcriptional regulation of genes in the hippocampus; therefore, we aimed to determine how epigenetic DNA methylation mechanisms affect learning-induced transcription of memory-permissive genes in the epileptic hippocampus.
  
  
  METHODS
  Using the kainate rodent model of TLE and focusing on the brain-derived neurotrophic factor (Bdnf) gene as a candidate of DNA methylation-mediated transcription, we analyzed DNA methylation levels in epileptic rats following learning. After detection of aberrant DNA methylation at the Bdnf gene, we investigated functional effects of altered DNA methylation on hippocampus-dependent memory formation in our TLE rodent model.
  
  
  RESULTS
  We found that behaviorally driven BdnfDNA methylation was associated with hippocampus-dependent memory deficits. Bisulfite sequencing revealed that decreased BdnfDNA methylation levels strongly correlated with abnormally high levels of BdnfmRNA in the epileptic hippocampus during memory consolidation. Methyl supplementation via methionine (Met) increased BdnfDNA methylation and reduced BdnfmRNA levels in the epileptic hippocampus during memory consolidation. Met administration reduced interictal spike activity, increased theta rhythm power, and reversed memory deficits in epileptic animals. The rescue effect of Met treatment on learning-induced BdnfDNA methylation, Bdnf gene expression, and hippocampus-dependent memory, were attenuated by DNA methyltransferase blockade.
  
  
  CONCLUSIONS
  Our findings suggest that manipulation of DNA methylation in the epileptic hippocampus should be considered as a viable treatment option to ameliorate memory impairments associated with TLE.
authors.affiliation: Department of Neurobiology, University of Alabama - Birmingham Birmingham, Alabama.
authors.forename: R Ryley
authors.initials: RR
authors.lastname: Parrish
authors.affiliation: Department of Neurobiology, University of Alabama - Birmingham Birmingham, Alabama.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Buckingham
authors.affiliation: Department of Neurobiology, University of Alabama - Birmingham Birmingham, Alabama.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Mascia
authors.affiliation: Department of Neurobiology, University of Alabama - Birmingham Birmingham, Alabama.
authors.forename: Jarvis J
authors.initials: JJ
authors.lastname: Johnson
authors.affiliation: Department of Chemistry, Weber State University Ogden, Utah.
authors.forename: Michal M
authors.initials: MM
authors.lastname: Matyjasik
authors.affiliation: Department of Neurobiology, University of Alabama - Birmingham Birmingham, Alabama.
authors.forename: Roxanne M
authors.initials: RM
authors.lastname: Lockhart
authors.affiliation: Department of Neurobiology, University of Alabama - Birmingham Birmingham, Alabama.
authors.forename: Farah D
authors.initials: FD
authors.lastname: Lubin