Data di Pubblicazione:
2014
Citazione:
Epigenetic reprogramming of cortical neurons through alteration of dopaminergic circuits / K. Brami-Cherrier, A. Anzalone, M. Ramos, I. Forne, F. Macciardi, A. Imhof, E. Borrelli. - In: MOLECULAR PSYCHIATRY. - ISSN 1359-4184. - 19:11(2014), pp. 1193-1200. [10.1038/mp.2014.67]
Abstract:
Alterations of the dopaminergic system are associated with the cognitive and functional dysfunctions that characterize complex neuropsychiatric disorders. We modeled a dysfunctional dopaminergic system using mice with targeted ablation of dopamine (DA) D2 autoreceptors in mesencephalic dopaminergic neurons. Loss of D2 autoreceptors abolishes D2-mediated control of DA synthesis and release. Here, we show that this mutation leads to a profound alteration of the genomic landscape of neurons receiving dopaminergic afferents at distal sites, specifically in the prefrontal cortex. Indeed, we observed a remarkable downregulation of gene expression in this area of ∼2000 genes, which involves a widespread increase in the histone repressive mark H3K9me2/3. This reprogramming process is coupled to psychotic-like behaviors in the mutant mice. Importantly, chronic treatment with a DA agonist can revert the genomic phenotype. Thus, cortical neurons undergo a profound epigenetic reprogramming in response to dysfunctional D2 autoreceptor signaling leading to altered DA levels, a process that may underlie a number of neuropsychiatric disorders.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Animals; Autoreceptors; Corpus Striatum; Dopamine; Dopamine Agonists; Dopaminergic Neurons; Down-Regulation; Gene Expression; Histones; Mice, Transgenic; Prefrontal Cortex; Psychotic Disorders; Quinpirole; Receptors, Dopamine D2; Epigenesis, Genetic; Molecular Biology; Psychiatry and Mental Health; Cellular and Molecular Neuroscience
Elenco autori:
K. Brami Cherrier, A. Anzalone, M. Ramos, I. Forne, F. Macciardi, A. Imhof, E. Borrelli
Link alla scheda completa: