TY - JOUR
T1 - Roles of Heat Shock Factor 1 in Neuronal Response to Fetal Environmental Risks and Its Relevance to Brain Disorders
AU - Hashimoto-Torii, Kazue
AU - Torii, Masaaki
AU - Fujimoto, Mitsuaki
AU - Nakai, Akira
AU - ElFatimy, Rachid
AU - Mezger, Valerie
AU - Ju, Min J.
AU - Ishii, Seiji
AU - Chao, Shih-Hui
AU - Brennand, Kristen J.
AU - Gage, Fred H.
AU - Rakic, Pasko
N1 - Funding Information:
We thank S. Rodriguez and M. Pappy for technical assistance and the Yale Statistical Clinic for technical advice. This work was supported by the Kavli Institute for Neuroscience at Yale (K.H.-T. and M.T.), R01-DA023999, R01NS014841 (P.R.), Brain & Behavior Research Foundation (K.H.-T., M.T., and K.J.B.), CTSI-CN, K99/R00-AA018387 (K.H.-T.), Institut de Recherche sur les Boissons (V.M. and R.E.), R01 MH101454 and the New York Stem Cell Foundation (K.J.B.), and CIRM Grant RL1-00649-1, the G. Harold & Leila Y. Mathers Foundation, the JPB Foundation, the Leona M. and Harry B. Helmsley Charitable Trust, Annette Merle-Smith, and Robert and Mary Jane Engman (F.G.).
PY - 2014/5/7
Y1 - 2014/5/7
N2 - Prenatal exposure of the developing brain to various environmental challenges increases susceptibility tolate 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.
AB - Prenatal exposure of the developing brain to various environmental challenges increases susceptibility tolate 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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U2 - 10.1016/j.neuron.2014.03.002
DO - 10.1016/j.neuron.2014.03.002
M3 - Article
C2 - 24726381
AN - SCOPUS:84899930065
SN - 0896-6273
VL - 82
SP - 560
EP - 572
JO - Neuron
JF - Neuron
IS - 3
ER -