| Literature DB >> 28533418 |
Sanaz Bahari-Javan1,2, Hristo Varbanov3, Rashi Halder4, Eva Benito4, Lalit Kaurani1, Susanne Burkhardt1, Heike Anderson-Schmidt1,5, Ion Anghelescu6, Monika Budde1,5, Roman M Stilling2, Joan Costa7, Juan Medina7, Detlef E Dietrich8, Christian Figge9, Here Folkerts10, Katrin Gade1,5, Urs Heilbronner1,5, Manfred Koller11, Carsten Konrad12, Sara Y Nussbeck13, Harald Scherk14, Carsten Spitzer15, Sebastian Stierl16, Judith Stöckel16, Andreas Thiel12, Martin von Hagen17, Jörg Zimmermann8,18, Antje Zitzelsberger10, Sybille Schulz18, Andrea Schmitt19,20, Ivana Delalle21, Peter Falkai1,20, Thomas G Schulze1,5, Alexander Dityatev3, Farahnaz Sananbenesi2, André Fischer22,4.
Abstract
Schizophrenia is a devastating disease that arises on the background of genetic predisposition and environmental risk factors, such as early life stress (ELS). In this study, we show that ELS-induced schizophrenia-like phenotypes in mice correlate with a widespread increase of histone-deacetylase 1 (Hdac1) expression that is linked to altered DNA methylation. Hdac1 overexpression in neurons of the medial prefrontal cortex, but not in the dorsal or ventral hippocampus, mimics schizophrenia-like phenotypes induced by ELS. Systemic administration of an HDAC inhibitor rescues the detrimental effects of ELS when applied after the manifestation of disease phenotypes. In addition to the hippocampus and prefrontal cortex, mice subjected to ELS exhibit increased Hdac1 expression in blood. Moreover, Hdac1 levels are increased in blood samples from patients with schizophrenia who had encountered ELS, compared with patients without ELS experience. Our data suggest that HDAC1 inhibition should be considered as a therapeutic approach to treat schizophrenia.Entities:
Keywords: HDAC inhibitor; early life stress; histone-deacetylases; personalized medicine; schizophrenia
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Year: 2017 PMID： 28533418 PMCID： PMC5468618 DOI： 10.1073/pnas.1613842114
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205