title: Roles of heat shock factor 1 in neuronal response to fetal environmental risks and its relevance to brain disorders.
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.
authors.affiliation: Department 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.
authors.forename: Kazue
authors.initials: K
authors.lastname: Hashimoto-Torii
authors.affiliation: Department 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.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Torii
authors.affiliation: Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, 755-8505 Ube, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, 755-8505 Ube, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakai
authors.affiliation: CNRS, UMR7216 Epigenetics and Cell Fate, 75205 Paris, France; University Paris Diderot, 75013 Paris, France.
authors.forename: Rachid
authors.initials: R
authors.lastname: El Fatimy
authors.affiliation: CNRS, UMR7216 Epigenetics and Cell Fate, 75205 Paris, France; University Paris Diderot, 75013 Paris, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Mezger
authors.affiliation: Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Min J
authors.initials: MJ
authors.lastname: Ju
authors.affiliation: Center for Neuroscience Research, Children's National Medical Center, Washington, DC 20010, USA.
authors.forename: Seiji
authors.initials: S
authors.lastname: Ishii
authors.affiliation: Center for Biosignatures Discovery Automation, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Shih-Hui
authors.initials: SH
authors.lastname: Chao
authors.affiliation: The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Brennand
authors.affiliation: The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
authors.affiliation: Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: pasko.rakic@yale.edu.
authors.forename: Pasko
authors.initials: P
authors.lastname: Rakic
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000196:embryology / Q000209:etiology / Q000503:physiopathology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D004781:Environmental Exposure; D000431:Ethanol / Q000633:toxicity; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000503:physiopathology; D000076249:Heat Shock Transcription Factors; D006801:Humans; D008767:Methylmercury Compounds / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D009924:Organ Culture Techniques; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000503:physiopathology*; D012640:Seizures / Q000150:complications / Q000503:physiopathology; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D008767:Methylmercury Compounds; D014157:Transcription Factors; D000431:Ethanol
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