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

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


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.

Publication types

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

MeSH terms

  • Animals
  • Brain Diseases / embryology
  • Brain Diseases / etiology
  • Brain Diseases / physiopathology*
  • DNA-Binding Proteins / physiology*
  • Environmental Exposure*
  • Ethanol / toxicity
  • Female
  • Fetus / drug effects
  • Fetus / physiopathology
  • Heat Shock Transcription Factors
  • Humans
  • Methylmercury Compounds / toxicity
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / drug effects
  • Neurons / pathology
  • Neurons / physiology*
  • Organ Culture Techniques
  • Pregnancy
  • Prenatal Exposure Delayed Effects / etiology
  • Prenatal Exposure Delayed Effects / physiopathology*
  • Seizures / complications
  • Seizures / physiopathology
  • Transcription Factors / physiology*


  • DNA-Binding Proteins
  • HSF1 protein, human
  • Heat Shock Transcription Factors
  • Hsf1 protein, mouse
  • Methylmercury Compounds
  • Transcription Factors
  • Ethanol