DNA methylation in post-mitotic neurons is reported to serve a variety of 
functions from survival during development to the consolidation of memory. Of 
particular interest with regards neuronal functioning is the change in 
site-specific methylation of a variety of gene promoters in the context of 
neuronal depolarization and the coding of new information. We examined the 
expression of DNMT1 and DNMT3a, representative of a maintenance and de novo 
methyltransferase respectively, in response to in-vitro depolarization of 
cortical neurons, using standard techniques such as high potassium (KCl) or the 
sodium channel agonist veratridine. KCl and veratridine mediated depolarization 
caused a modest but significant and replicable reduction in the mRNA and protein 
expression of both DNMTs that was time and dose dependent. These effects were 
supported by parallel increases in the mRNA expression of BDNF exon-1 and exon-4 
as a typical response of neurons to depolarization and to rule out the 
possibility of impaired transcriptional activity as a trivial explanation. In 
addition to effects on mRNA and protein expression, functional DNA 
methyltransferase activity was reduced in nuclear protein extracts from cells 
exposed to a depolarization condition. Also, these changes could not be 
explained by differential neuronal loss as measured by cell viability 
cytochemistry. Our results support the idea that a reduction in DNA 
methyltransferase activity in the activated and depolarized neuron could 
contribute to the enhanced intensity and multiplicity of gene expression 
frequently reported.