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Roles of Heat Shock Factor 1 in Neuronal Response to Fetal Environmental Risks and Its Relevance to Brain Disorders

descriptionPublicationkeyboard_double_arrow_right Article , Other literature type , Journal 01 May 2014Publisher:Elsevier BVJournal:Neuron, volume 82, pages 560-572 (issn: 0896-6273,

Copyright policy )Funded by:NIH | Origin of Cortical Specie..., NIH | Neurogenetic Processes in..., NIH | Mechanisms leading to cor... +2 projects

Authors: Valérie Mezger; Valérie Mezger; Pasko Rakic; Seiji Ishii; Mitsuaki Fujimoto; Shih-hui Chao; Akira Nakai; +9 Authors

doi: 10.1016/j.neuron.2014.03.002

pmid: 24726381

pmc: PMC4051437

Roles of Heat Shock Factor 1 in Neuronal Response to Fetal Environmental Risks and Its Relevance to Brain Disorders

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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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Keywords

[SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Neuroscience(all), Mice, Fetus, Organ Culture Techniques, Heat Shock Transcription Factors, Pregnancy, Seizures, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Mice, Knockout, Neurons, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Brain Diseases, Ethanol, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Environmental Exposure, Methylmercury Compounds, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], DNA-Binding Proteins, Mice, Inbred C57BL, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Prenatal Exposure Delayed Effects, Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Transcription Factors

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	citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).	105
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	influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).	Top 10%
	impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.	Top 1%