气候变化领域集成服务门户(CCPortal): Impact of prenatal maternal cytokine exposure on sex differences in brain circuitry regulating stress in offspring 45 years later

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DOI	10.1073/pnas.2014464118
	Impact of prenatal maternal cytokine exposure on sex differences in brain circuitry regulating stress in offspring 45 years later
	Goldstein J.M.; Cohen J.E.; Mareckova K.; Holsen L.; Whitfield-Gabrieli S.; Gilman S.E.; Buka S.L.; Hornig M.
发表日期	2021
ISSN	00278424
卷号	118 期号:15
英文摘要	Stress is associated with numerous chronic diseases, beginning in fetal development with in utero exposures (prenatal stress) impacting offspring's risk for disorders later in life. In previous studies, we demonstrated adverse maternal in utero immune activity on sex differences in offspring neurodevelopment at age seven and adult risk for major depression and psychoses. Here, we hypothesized that in utero exposure to maternal proinflammatory cytokines has sex-dependent effects on specific brain circuitry regulating stress and immune function in the offspring that are retained across the lifespan. Using a unique prenatal cohort, we tested this hypothesis in 80 adult offspring, equally divided by sex, followed from in utero development to midlife. Functional MRI results showed that exposure to proinflammatory cytokines in utero was significantly associated with sex differences in brain activity and connectivity during response to negative stressful stimuli 45 y later. Lower maternal TNF-α levels were significantly associated with higher hypothalamic activity in both sexes and higher functional connectivity between hypothalamus and anterior cingulate only in men. Higher prenatal levels of IL-6 were significantly associated with higher hippocampal activity in women alone. When examined in relation to the anti-inflammatory effects of IL-10, the ratio TNF-α:IL-10 was associated with sex-dependent effects on hippocampal activity and functional connectivity with the hypothalamus. Collectively, results suggested that adverse levels of maternal in utero proinflammatory cytokines and the balance of pro- to anti-inflammatory cytokines impact brain development of offspring in a sexually dimorphic manner that persists across the lifespan. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Functional brain imaging; Prenatal immune programming; Prenatal stress; Sex; Stress circuitry
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179890
作者单位	Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States; Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA 02114, United States; Athinoula Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, United States; Central European Institute of Technology, Masaryk University, Brno, 601 77, Czech Republic; Division of Women's Health, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States; Northeastern University Interdisciplinary Science and Engineering Complex, Northeastern University, Boston, MA 02120, United States; Social and Behavioral Sciences Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21...
推荐引用方式 GB/T 7714	Goldstein J.M.,Cohen J.E.,Mareckova K.,et al. Impact of prenatal maternal cytokine exposure on sex differences in brain circuitry regulating stress in offspring 45 years later[J],2021,118(15).
APA	Goldstein J.M..,Cohen J.E..,Mareckova K..,Holsen L..,Whitfield-Gabrieli S..,...&Hornig M..(2021).Impact of prenatal maternal cytokine exposure on sex differences in brain circuitry regulating stress in offspring 45 years later.Proceedings of the National Academy of Sciences of the United States of America,118(15).
MLA	Goldstein J.M.,et al."Impact of prenatal maternal cytokine exposure on sex differences in brain circuitry regulating stress in offspring 45 years later".Proceedings of the National Academy of Sciences of the United States of America 118.15(2021).