Impact of prenatal maternal cytokine exposure on sex differences in brain circuitry regulating stress in offspring 45 years later
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F21%3A00124230" target="_blank" >RIV/00216224:14740/21:00124230 - isvavai.cz</a>
Result on the web
<a href="https://www.pnas.org/content/pnas/118/15/e2014464118.full.pdf" target="_blank" >https://www.pnas.org/content/pnas/118/15/e2014464118.full.pdf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1073/pnas.2014464118" target="_blank" >10.1073/pnas.2014464118</a>
Alternative languages
Result language
angličtina
Original language name
Impact of prenatal maternal cytokine exposure on sex differences in brain circuitry regulating stress in offspring 45 years later
Original language description
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-a 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-alpha: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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
<a href="/en/project/EE2.3.30.0009" target="_blank" >EE2.3.30.0009: Employment of Newly Graduated Doctors of Science for Scientific Excellence</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Proceedings of the National Academy of Sciences of the United States of America
ISSN
0027-8424
e-ISSN
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Volume of the periodical
118
Issue of the periodical within the volume
15
Country of publishing house
US - UNITED STATES
Number of pages
8
Pages from-to
„e2014464118“
UT code for WoS article
000641176100005
EID of the result in the Scopus database
2-s2.0-85104235036