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Neuron. 2014 May 7;82(3):560-72. doi: 10.1016/j.neuron.2014.03.002. Epub 2014 Apr 10.

Roles of heat shock factor 1 in neuronal response to fetal environmental risks and its relevance to brain disorders.

Author information

  • 1Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Neuroscience Research, Children's National Medical Center, Washington, DC 20010, USA; Department of Pediatrics, Pharmacology and Physiology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20010, USA. Electronic address: khtorii@cnmc.org.
  • 2Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Neuroscience Research, Children's National Medical Center, Washington, DC 20010, USA; Department of Pediatrics, Pharmacology and Physiology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20010, USA; Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
  • 3Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, 755-8505 Ube, Japan.
  • 4CNRS, UMR7216 Epigenetics and Cell Fate, 75205 Paris, France; University Paris Diderot, 75013 Paris, France.
  • 5Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.
  • 6Center for Neuroscience Research, Children's National Medical Center, Washington, DC 20010, USA.
  • 7Center for Biosignatures Discovery Automation, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
  • 8The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
  • 9Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: pasko.rakic@yale.edu.

Abstract

Prenatal exposure of the developing brain to various environmental challenges increases susceptibility to late onset of neuropsychiatric dysfunction; still, the underlying mechanisms remain obscure. Here we show that exposure of embryos to a variety of environmental factors such as alcohol, methylmercury, and maternal seizure activates HSF1 in cerebral cortical cells. Furthermore, Hsf1 deficiency in the mouse cortex exposed in utero to subthreshold levels of these challenges causes structural abnormalities and increases seizure susceptibility after birth. In addition, we found that human neural progenitor cells differentiated from induced pluripotent stem cells derived from schizophrenia patients show higher variability in the levels of HSF1 activation induced by environmental challenges compared to controls. We propose that HSF1 plays a crucial role in the response of brain cells to prenatal environmental insults and may be a key component in the pathogenesis of late-onset neuropsychiatric disorders.

Copyright © 2014 Elsevier Inc. All rights reserved.

PMID:
24726381
[PubMed - indexed for MEDLINE]
PMCID:
PMC4051437
[Available on 2015/5/7]
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