PMID- 25909085
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150424
LR  - 20220409
IS  - 2328-9503 (Print)
IS  - 2328-9503 (Electronic)
IS  - 2328-9503 (Linking)
VI  - 2
IP  - 4
DP  - 2015 Apr
TI  - Methionine increases BDNF DNA methylation and improves memory in epilepsy.
PG  - 401-16
LID - 10.1002/acn3.183 [doi]
AB  - 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. INTERPRETATION: 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.
FAU - Parrish, R Ryley
AU  - Parrish RR
AD  - Department of Neurobiology, University of Alabama - Birmingham Birmingham, 
      Alabama.
FAU - Buckingham, Susan C
AU  - Buckingham SC
AD  - Department of Neurobiology, University of Alabama - Birmingham Birmingham, 
      Alabama.
FAU - Mascia, Katherine L
AU  - Mascia KL
AD  - Department of Neurobiology, University of Alabama - Birmingham Birmingham, 
      Alabama.
FAU - Johnson, Jarvis J
AU  - Johnson JJ
AD  - Department of Neurobiology, University of Alabama - Birmingham Birmingham, 
      Alabama.
FAU - Matyjasik, Michal M
AU  - Matyjasik MM
AD  - Department of Chemistry, Weber State University Ogden, Utah.
FAU - Lockhart, Roxanne M
AU  - Lockhart RM
AD  - Department of Neurobiology, University of Alabama - Birmingham Birmingham, 
      Alabama.
FAU - Lubin, Farah D
AU  - Lubin FD
AD  - Department of Neurobiology, University of Alabama - Birmingham Birmingham, 
      Alabama.
LA  - eng
GR  - P30 HD038985/HD/NICHD NIH HHS/United States
GR  - K99 MH082106/MH/NIMH NIH HHS/United States
GR  - R01 MH097909/MH/NIMH NIH HHS/United States
GR  - F32 NS048811/NS/NINDS NIH HHS/United States
GR  - R00 MH082106/MH/NIMH NIH HHS/United States
GR  - R21 NS090250/NS/NINDS NIH HHS/United States
GR  - R56 MH097909/MH/NIMH NIH HHS/United States
PT  - Journal Article
DEP - 20150312
PL  - United States
TA  - Ann Clin Transl Neurol
JT  - Annals of clinical and translational neurology
JID - 101623278
PMC - PMC4402085
EDAT- 2015/04/25 06:00
MHDA- 2015/04/25 06:01
PMCR- 2015/03/12
CRDT- 2015/04/25 06:00
PHST- 2015/01/19 00:00 [received]
PHST- 2015/01/20 00:00 [accepted]
PHST- 2015/04/25 06:00 [entrez]
PHST- 2015/04/25 06:00 [pubmed]
PHST- 2015/04/25 06:01 [medline]
PHST- 2015/03/12 00:00 [pmc-release]
AID - 10.1002/acn3.183 [doi]
PST - ppublish
SO  - Ann Clin Transl Neurol. 2015 Apr;2(4):401-16. doi: 10.1002/acn3.183. Epub 2015 
      Mar 12.