title: Where Environment Meets Cognition: A Focus on Two Developmental Intellectual Disability Disorders.
abstract: One of the most challenging questions in neuroscience is to dissect how learning and memory, the foundational pillars of cognition, are grounded in stable, yet plastic, gene expression states. All known epigenetic mechanisms such as DNA methylation and hydroxymethylation, histone modifications, chromatin remodelling, and noncoding RNAs regulate brain gene expression, both during neurodevelopment and in the adult brain in processes related to cognition. On the other hand, alterations in the various components of the epigenetic machinery have been linked to well-known causes of intellectual disability disorders (IDDs). Two examples are Down Syndrome (DS) and Fragile X Syndrome (FXS), where global and local epigenetic alterations lead to impairments in synaptic plasticity, memory, and learning. Since epigenetic modifications are reversible, it is theoretically possible to use epigenetic drugs as cognitive enhancers for the treatment of IDDs. Epigenetic treatments act in a context specific manner, targeting different regions based on cell and state specific chromatin accessibility, facilitating the establishment of the lost balance. Here, we discuss epigenetic studies of IDDs, focusing on DS and FXS, and the use of epidrugs in combinatorial therapies for IDDs.
authors.affiliation: Cellular and Systems Neurobiology, Systems Biology Program, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain; Pompeu Fabra University, 08003 Barcelona, Spain.
authors.forename: I
authors.identifier: 0000-0003-4128-2561
authors.initials: I
authors.lastname: De Toma
authors.affiliation: Cellular and Systems Neurobiology, Systems Biology Program, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain; Pompeu Fabra University, 08003 Barcelona, Spain.
authors.forename: L
authors.identifier: 0000-0003-2036-2204
authors.initials: L
authors.lastname: Manubens-Gil
authors.affiliation: Pompeu Fabra University, 08003 Barcelona, Spain; Genomic and Epigenomic Variation in Disease Group, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Ossowski
authors.affiliation: Cellular and Systems Neurobiology, Systems Biology Program, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain; Pompeu Fabra University, 08003 Barcelona, Spain.
authors.forename: M
authors.identifier: 0000-0003-0853-6865
authors.initials: M
authors.lastname: Dierssen
mesh_terms: D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D019175:DNA Methylation / Q000235:genetics; D004314:Down Syndrome / Q000235:genetics* / Q000523:psychology / Q000628:therapy; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics* / Q000523:psychology / Q000628:therapy; D059647:Gene-Environment Interaction; D015316:Genetic Therapy / Q000379:methods / Q000639:trends*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000523:psychology / Q000628:therapy; D054730:Protein Interaction Domains and Motifs / Q000235:genetics
chemical_list: D000975:Antioxidants; D002392:Catechin; C045651:epigallocatechin gallate