Thanks to a research carried out at the Laboratory of Biology BIO@SNS of the Scuola Normale Superiore in Pisa and at the Institute of Neuroscience of the National Research Council in Pisa, we can face this important question. The role of the epigenetic factors is explained in the article published on Nature Neuroscience, Experience-dependent DNA methylation regulates plasticity in the developing visual cortex, by Paola Tognini, Debora Napoli, Jonida Tola, Davide Silingardi, Floriana Della Ragione, Maurizio D’Esposito & Tommaso Pizzorusso. First co-authors are Paola Tognini, PhD at the Scuola Normale Superiore and now post-doc at the Institute of Neuroscience of the National Research Council and Debora Napoli, PhD student of the PhD Program in Neurosciences of the Scuola Normale, while coordinator of the research is prof. Tommaso Pizzorusso, Associate professor of Psicobiology at the University of Florence and faculty member of the Neurosciences PhD Program of the Scuola Normale.

The research reveals a previously unknown role of mechanisms controlling DNA methylation as molecular mediators in the experience-dependent refinement of cortical circuits during development, providing a possible mechanistic framework to understand why factors involving DNA methylation regulation could have deleterious effects on synaptic development in animal models and neuropsychiatric symptoms in humans.

DNA Methylation is an epigenetic repressor mark for transcription, dynamically regulated in neurons. Researchers analyzed visual experience regulation of DNA methylation and its involvement in ocular dominance plasticity of the developing visual cortex and they found out that monocular deprivation modulated the expression of factors controlling DNA methylation such as the enzyme DNA methyltransferase (DNMT) and exerted effects expression of specific plasticity genes. They demonstrated that inhibition of DNMT blocked molecular and functional effects of monocular deprivation, partially reversing the monocular deprivation transcriptional program.

These results show a new mechanism involving DNA methylation as molecular mediator of developing cortical brain circuitry and show how mutation involving DNA methylation enzymes could be key factors of neuropsychiatric diseases

The research has been carried out within MIUR-CNR EPIGEN project, which aims at analyzing how epigenetic mechanisms regulate biological processes, determine phenotypic variation and contribute to the onset and progression of diseases. The institutions involved are the University of Florence, the Institute of Neuroscience of the Italian National Research Council in Pisa, the Laboratory of Biology BIO@SNS of the Scuola Normale Superiore in Pisa, and the Institute of Genetics and Biophysics of the Italian National Research Council of Naples.