3 years ago

HDAC1 links early life stress to schizophrenia-like phenotypes [Neuroscience]

HDAC1 links early life stress to schizophrenia-like phenotypes [Neuroscience]
Roman M. Stilling, Monika Budde, Juan Medina, Andreas Thiel, Ion Anghelescu, Urs Heilbronner, Judith Stockel, Andre Fischer, Hristo Varbanov, Sara Y. Nussbeck, Christian Figge, Harald Scherk, Antȷe Zitzelsberger, Joan Costa, Manfred Koller, Jorg Zimmermann, Farahnaz Sananbenesi, Eva Benito, Sybille Schulz, Thomas G. Schulze, Carsten Konrad, Alexander Dityatev, Rashi Halder, Lalit Kaurani, Andrea Schmitt, Here Folkerts, Martin von Hagen, Heike Anderson–Schmidt, Sanaz Bahari–Javan, Detlef E. Dietrich, Sebastian Stierl, Ivana Delalle, Carsten Spitzer, Peter Falkai, Katrin Gade, Susanne Burkhardt

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.

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