title: Detection of vulnerable neurons damaged by environmental insults in utero.
abstract: Development of prognostic biomarkers for the detection of prenatally damaged neurons before manifestations of postnatal disorders is an essential step for prevention and treatment of susceptible individuals. We have developed a versatile fluorescence reporter system in mice enabling detection of Heat Shock Factor 1 activation in response to prenatal cellular damage caused by exposure to various harmful chemical or physical agents. Using an intrautero electroporation-mediated reporter assay and transgenic reporter mice, we are able to identify neurons that survive prenatal exposure to harmful agents but remain vulnerable in postnatal life. This system may provide a powerful tool for exploring the pathogenesis and treatment of multiple disorders caused by exposure to environmental stress before symptoms become manifested, exacerbated, and/or irreversible.
authors.affiliation: Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010.|Department of Pediatrics, Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052.|Department of Neurobiology, School of Medicine, Yale University, New Haven, CT 06510.|Kavli Institute for Neuroscience, School of Medicine, Yale University, New Haven, CT 06510.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Torii
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06510.|Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT 06516.|Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido 060-8556, Japan.
authors.forename: Masanori
authors.identifier: 0000-0001-7961-9698
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06510.|Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT 06516.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Chang
authors.affiliation: Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010.
authors.forename: Seiji
authors.initials: S
authors.lastname: Ishii
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06510.|Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT 06516.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Waxman
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06510.|Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT 06516.
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Kocsis
authors.affiliation: Department of Neurobiology, School of Medicine, Yale University, New Haven, CT 06510; khtorii@cnmc.org pasko.rakic@yale.edu.|Kavli Institute for Neuroscience, School of Medicine, Yale University, New Haven, CT 06510.
authors.forename: Pasko
authors.initials: P
authors.lastname: Rakic
authors.affiliation: Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010; khtorii@cnmc.org pasko.rakic@yale.edu.|Department of Pediatrics, Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052.|Department of Neurobiology, School of Medicine, Yale University, New Haven, CT 06510.|Kavli Institute for Neuroscience, School of Medicine, Yale University, New Haven, CT 06510.
authors.forename: Kazue
authors.initials: K
authors.lastname: Hashimoto-Torii
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018274:Electroporation; D004622:Embryo, Mammalian; D000431:Ethanol / Q000633:toxicity; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D000076249:Heat Shock Transcription Factors / Q000235:genetics* / Q000378:metabolism; D018869:Heat-Shock Response / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009538:Nicotine / Q000633:toxicity; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D020218:Response Elements; D013498:Suramin / Q000633:toxicity
chemical_list: D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D008164:Luminescent Proteins; C413663:fluorescent protein 583; D000431:Ethanol; D013498:Suramin; D009538:Nicotine
keywords: cerebral cortex; development; environmental stress; heat shock signaling; reporter