Neonatal immune challenge poses a sex-specific risk for epigenetic microglial reprogramming and behavioral impairment.

Autor: Schwabenland M; Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Mossad O; Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany., Sievert A; Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Peres AG; Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Ringel E; Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Baasch S; Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Kolter J; Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Cascone G; Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Dokalis N; Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany., Vlachos A; Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Center for Basics in Neuromodulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, Freiburg, Germany., Ruzsics Z; Institute for Virology, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany., Henneke P; Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Center for Pediatrics and Adolescent Medicine, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; CIBSS Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany., Prinz M; Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Center for Basics in Neuromodulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS-Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany., Blank T; Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany. thomas.blank@uniklinik-freiburg.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 May 11; Vol. 14 (1), pp. 2721. Date of Electronic Publication: 2023 May 11.
DOI: 10.1038/s41467-023-38373-0
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: