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

Neuron (2014-04-15)
Kazue Hashimoto-Torii, Masaaki Torii, Mitsuaki Fujimoto, Akira Nakai, Rachid El Fatimy, Valerie Mezger, Min J Ju, Seiji Ishii, Shih-Hui Chao, Kristen J Brennand, Fred H Gage, Pasko Rakic
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.

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