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Prenatal Environmental Stressors Impair Postnatal Microglia Function and Adult Behavior in Males

View ORCID ProfileCarina L. Block, Oznur Eroglu, Stephen D. Mague, View ORCID ProfileChaichontat Sriworarat, Cameron Blount, Karen E. Malacon, Kathleen A. Beben, Nkemdilim Ndubuizu, Austin Talbot, Neil M. Gallagher, Young Chan Jo, Timothy Nyangacha, View ORCID ProfileDavid E. Carlson, View ORCID ProfileKafui Dzirasa, View ORCID ProfileCagla Eroglu, View ORCID ProfileStaci D. Bilbo
doi: https://doi.org/10.1101/2020.10.15.336669
Carina L. Block
1Department of Psychology and Neuroscience, Trinity College of Arts and Sciences, Duke University, Durham, NC 27710, United States
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  • ORCID record for Carina L. Block
Oznur Eroglu
2Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, United States
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Stephen D. Mague
3Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, United States
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Chaichontat Sriworarat
2Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, United States
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Cameron Blount
3Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, United States
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Karen E. Malacon
1Department of Psychology and Neuroscience, Trinity College of Arts and Sciences, Duke University, Durham, NC 27710, United States
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Kathleen A. Beben
1Department of Psychology and Neuroscience, Trinity College of Arts and Sciences, Duke University, Durham, NC 27710, United States
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Nkemdilim Ndubuizu
3Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, United States
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Austin Talbot
4Department of Statistical Science, Duke University, Durham, NC 27710, United States
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Neil M. Gallagher
3Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, United States
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Young Chan Jo
1Department of Psychology and Neuroscience, Trinity College of Arts and Sciences, Duke University, Durham, NC 27710, United States
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Timothy Nyangacha
3Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, United States
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David E. Carlson
5Department of Civil and Environmental Engineering, Duke University, Durham, NC 27710, United States
6Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC 27710, United States
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Kafui Dzirasa
3Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, United States
7Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, United States
8Duke Institute for Brain Sciences (DIBS), Durham, NC 27710, United States
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  • For correspondence: staci.bilbo@duke.edu cagla.eroglu@duke.edu kafui.dzirasa@duke.edu
Cagla Eroglu
2Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, United States
3Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, United States
8Duke Institute for Brain Sciences (DIBS), Durham, NC 27710, United States
9Regeneration Next Initiative, Duke University, Durham, NC 27710, United States
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  • For correspondence: staci.bilbo@duke.edu cagla.eroglu@duke.edu kafui.dzirasa@duke.edu
Staci D. Bilbo
1Department of Psychology and Neuroscience, Trinity College of Arts and Sciences, Duke University, Durham, NC 27710, United States
3Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, United States
8Duke Institute for Brain Sciences (DIBS), Durham, NC 27710, United States
10Lurie Center for Autism, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, United States
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  • For correspondence: staci.bilbo@duke.edu cagla.eroglu@duke.edu kafui.dzirasa@duke.edu
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Abstract

Gestational exposure to environmental toxins and socioeconomic stressors are epidemiologically linked to neurodevelopmental disorders with strong male-bias, such as autism. We modeled these prenatal risk factors in mice, by co-exposing pregnant dams to an environmental pollutant and limited-resource stress, which robustly activated the maternal immune system. Only male offspring displayed long-lasting behavioral abnormalities and alterations in the activity of brain networks encoding social interactions. Cellularly, prenatal stressors diminished microglial function within the anterior cingulate cortex, a central node of the social coding network, in males during early postnatal development. Genetic ablation of microglia during the same critical period mimicked the impact of prenatal stressors on a male-specific behavior, indicating that environmental stressors alter neural circuit formation in males via impairing microglia function during development.

Competing Interest Statement

The authors have declared no competing interest.

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Posted October 19, 2020.
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Prenatal Environmental Stressors Impair Postnatal Microglia Function and Adult Behavior in Males
Carina L. Block, Oznur Eroglu, Stephen D. Mague, Chaichontat Sriworarat, Cameron Blount, Karen E. Malacon, Kathleen A. Beben, Nkemdilim Ndubuizu, Austin Talbot, Neil M. Gallagher, Young Chan Jo, Timothy Nyangacha, David E. Carlson, Kafui Dzirasa, Cagla Eroglu, Staci D. Bilbo
bioRxiv 2020.10.15.336669; doi: https://doi.org/10.1101/2020.10.15.336669
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Prenatal Environmental Stressors Impair Postnatal Microglia Function and Adult Behavior in Males
Carina L. Block, Oznur Eroglu, Stephen D. Mague, Chaichontat Sriworarat, Cameron Blount, Karen E. Malacon, Kathleen A. Beben, Nkemdilim Ndubuizu, Austin Talbot, Neil M. Gallagher, Young Chan Jo, Timothy Nyangacha, David E. Carlson, Kafui Dzirasa, Cagla Eroglu, Staci D. Bilbo
bioRxiv 2020.10.15.336669; doi: https://doi.org/10.1101/2020.10.15.336669

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