Detection of vulnerable neurons damaged by environmental insults in utero

Proc Natl Acad Sci U S A. 2017 Feb 28;114(9):2367-2372. doi: 10.1073/pnas.1620641114. Epub 2017 Jan 25.

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.

Keywords: cerebral cortex; development; environmental stress; heat shock signaling; reporter.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Electroporation
  • Embryo, Mammalian
  • Ethanol / toxicity
  • Female
  • Flow Cytometry
  • Gene Expression Regulation
  • Genes, Reporter
  • Heat Shock Transcription Factors / genetics*
  • Heat Shock Transcription Factors / metabolism
  • Heat-Shock Response / genetics
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Nicotine / toxicity
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / diagnosis*
  • Prenatal Exposure Delayed Effects / genetics*
  • Prenatal Exposure Delayed Effects / pathology
  • Response Elements*
  • Suramin / toxicity

Substances

  • Heat Shock Transcription Factors
  • Hsf1 protein, mouse
  • Luminescent Proteins
  • fluorescent protein 583
  • Ethanol
  • Suramin
  • Nicotine