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Cortical DNA methylation maintains remote memory

2010; Nature Portfolio; Volume: 13; Issue: 6 Linguagem: Inglês

10.1038/nn.2560

1546-1726

Courtney A. Miller, Cristin F. Gavin, Jason White, R. Ryley Parrish, Avinash Honasoge, Christopher R Yancey, Ivonne Rivera, María Dolores Rubio, Gavin Rumbaugh, J. David Sweatt,

Identity, Memory, and Therapy

The authors report that persistent, gene-specific hypermethylation is induced by associative learning and that inhibition of methylation long after learning disrupts remote memory. This suggests that DNA methylation may be a mechanism for preserving long-lasting memories. A behavioral memory's lifetime represents multiple molecular lifetimes, suggesting the necessity for a self-perpetuating signal. One candidate is DNA methylation, a transcriptional repression mechanism that maintains cellular memory throughout development. We found that persistent, gene-specific cortical hypermethylation was induced in rats by a single, hippocampus-dependent associative learning experience and pharmacologic inhibition of methylation 1 month after learning disrupted remote memory. We propose that the adult brain utilizes DNA methylation to preserve long-lasting memories.