Neonatal immune challenge poses a sex-specific risk for epigenetic microglial reprogramming and behavioral impairment
Abstract While the precise processes underlying a sex bias in the development of central nervous system (CNS) disorders are unknown, there is growing evidence that an early life immune activation can contribute to the disease pathogenesis. When we mimicked an early systemic viral infection or applie...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-38373-0 |
| _version_ | 1797827416529305600 |
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| author | Marius Schwabenland Omar Mossad Annika Sievert Adam G. Peres Elena Ringel Sebastian Baasch Julia Kolter Giulia Cascone Nikolaos Dokalis Andreas Vlachos Zsolt Ruzsics Philipp Henneke Marco Prinz Thomas Blank |
| author_facet | Marius Schwabenland Omar Mossad Annika Sievert Adam G. Peres Elena Ringel Sebastian Baasch Julia Kolter Giulia Cascone Nikolaos Dokalis Andreas Vlachos Zsolt Ruzsics Philipp Henneke Marco Prinz Thomas Blank |
| author_sort | Marius Schwabenland |
| collection | DOAJ |
| description | Abstract While the precise processes underlying a sex bias in the development of central nervous system (CNS) disorders are unknown, there is growing evidence that an early life immune activation can contribute to the disease pathogenesis. When we mimicked an early systemic viral infection or applied murine cytomegalovirus (MCMV) systemically in neonatal female and male mice, only male adolescent mice presented behavioral deficits, including reduced social behavior and cognition. This was paralleled by an increased amount of infiltrating T cells in the brain parenchyma, enhanced interferon-γ (IFNγ) signaling, and epigenetic reprogramming of microglial cells. These microglial cells showed increased phagocytic activity, which resulted in abnormal loss of excitatory synapses within the hippocampal brain region. None of these alterations were seen in female adolescent mice. Our findings underscore the early postnatal period’s susceptibility to cause sex-dependent long-term CNS deficiencies following infections. |
| first_indexed | 2024-04-09T12:47:56Z |
| format | Article |
| id | doaj.art-022f19c530b44fd49b9880275f4ac107 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-09T12:47:56Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-022f19c530b44fd49b9880275f4ac1072023-05-14T11:21:07ZengNature PortfolioNature Communications2041-17232023-05-0114111910.1038/s41467-023-38373-0Neonatal immune challenge poses a sex-specific risk for epigenetic microglial reprogramming and behavioral impairmentMarius Schwabenland0Omar Mossad1Annika Sievert2Adam G. Peres3Elena Ringel4Sebastian Baasch5Julia Kolter6Giulia Cascone7Nikolaos Dokalis8Andreas Vlachos9Zsolt Ruzsics10Philipp Henneke11Marco Prinz12Thomas Blank13Institute of Neuropathology, Faculty of Medicine, University of FreiburgInstitute of Neuropathology, Faculty of Medicine, University of FreiburgInstitute of Neuropathology, Faculty of Medicine, University of FreiburgInstitute of Neuropathology, Faculty of Medicine, University of FreiburgInstitute of Neuropathology, Faculty of Medicine, University of FreiburgInstitute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center, University of Freiburg, Faculty of Medicine, University of FreiburgInstitute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center, University of Freiburg, Faculty of Medicine, University of FreiburgInstitute of Neuropathology, Faculty of Medicine, University of FreiburgInstitute of Neuropathology, Faculty of Medicine, University of FreiburgDepartment of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of FreiburgInstitute for Virology, Faculty of Medicine, Medical Center, University of FreiburgInstitute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center, University of Freiburg, Faculty of Medicine, University of FreiburgInstitute of Neuropathology, Faculty of Medicine, University of FreiburgInstitute of Neuropathology, Faculty of Medicine, University of FreiburgAbstract While the precise processes underlying a sex bias in the development of central nervous system (CNS) disorders are unknown, there is growing evidence that an early life immune activation can contribute to the disease pathogenesis. When we mimicked an early systemic viral infection or applied murine cytomegalovirus (MCMV) systemically in neonatal female and male mice, only male adolescent mice presented behavioral deficits, including reduced social behavior and cognition. This was paralleled by an increased amount of infiltrating T cells in the brain parenchyma, enhanced interferon-γ (IFNγ) signaling, and epigenetic reprogramming of microglial cells. These microglial cells showed increased phagocytic activity, which resulted in abnormal loss of excitatory synapses within the hippocampal brain region. None of these alterations were seen in female adolescent mice. Our findings underscore the early postnatal period’s susceptibility to cause sex-dependent long-term CNS deficiencies following infections.https://doi.org/10.1038/s41467-023-38373-0 |
| spellingShingle | Marius Schwabenland Omar Mossad Annika Sievert Adam G. Peres Elena Ringel Sebastian Baasch Julia Kolter Giulia Cascone Nikolaos Dokalis Andreas Vlachos Zsolt Ruzsics Philipp Henneke Marco Prinz Thomas Blank Neonatal immune challenge poses a sex-specific risk for epigenetic microglial reprogramming and behavioral impairment Nature Communications |
| title | Neonatal immune challenge poses a sex-specific risk for epigenetic microglial reprogramming and behavioral impairment |
| title_full | Neonatal immune challenge poses a sex-specific risk for epigenetic microglial reprogramming and behavioral impairment |
| title_fullStr | Neonatal immune challenge poses a sex-specific risk for epigenetic microglial reprogramming and behavioral impairment |
| title_full_unstemmed | Neonatal immune challenge poses a sex-specific risk for epigenetic microglial reprogramming and behavioral impairment |
| title_short | Neonatal immune challenge poses a sex-specific risk for epigenetic microglial reprogramming and behavioral impairment |
| title_sort | neonatal immune challenge poses a sex specific risk for epigenetic microglial reprogramming and behavioral impairment |
| url | https://doi.org/10.1038/s41467-023-38373-0 |
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