Brain region-specific alterations in gene expression trajectories in the offspring born from influenza A virus infected mice.

Autor: Liong S; Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia., Choy KHC; Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia., De Luca SN; Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia., Liong F; Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia., Coward-Smith M; Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia., Oseghale O; Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia., Miles MA; Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia., Vlahos R; Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia., Valant C; Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia., Nithianantharajah J; The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia; Department of Florey Neuroscience, University of Melbourne, Melbourne, VIC, Australia. Electronic address: jess.n@florey.edu.au., Pantelis C; The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia; Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia; Neuromedicines Discovery Centre, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia. Electronic address: cpant@unimelb.edu.au., Christopoulos A; Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia; ARC Centre for Cryo-electron Microscopy of Membrane Proteins, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia; Neuromedicines Discovery Centre, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia. Electronic address: Arthur.christopoulos@monash.edu., Selemidis S; Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia. Electronic address: Stavros.selemidis@rmit.edu.au.
Jazyk: angličtina
Zdroj: Brain, behavior, and immunity [Brain Behav Immun] 2024 Aug; Vol. 120, pp. 488-498. Date of Electronic Publication: 2024 Jun 24.
DOI: 10.1016/j.bbi.2024.06.025
Abstrakt: Influenza A virus (IAV) infection during pregnancy can increase the risk for neurodevelopmental disorders in the offspring, however, the underlying neurobiological mechanisms are largely unknown. To recapitulate viral infection, preclinical studies have traditionally focused on using synthetic viral mimetics, rather than live IAV, to examine consequences of maternal immune activation (MIA)-dependent processes on offspring. In contrast, few studies have used live IAV to assess effects on global gene expression, and none to date have addressed whether moderate IAV, mimicking seasonal influenza disease, alters normal gene expression trajectories in different brain regions across different stages of development. Herein, we show that moderate IAV infection during pregnancy, which causes mild maternal disease and no overt foetal complications in utero, induces lasting effects on the offspring into adulthood. We observed behavioural changes in adult offspring, including disrupted prepulse inhibition, dopaminergic hyper-responsiveness, and spatial recognition memory deficits. Gene profiling in the offspring brain from neonate to adolescence revealed persistent alterations to normal gene expression trajectories in the prefronal cortex, hippocampus, hypothalamus and cerebellum. Alterations were found in genes involved in inflammation and neurogenesis, which were predominately dysregulated in neonatal and early adolescent offspring. Notably, late adolescent offspring born from IAV infected mice displayed altered microglial morphology in the hippocampus. In conclusion, we show that moderate IAV during pregnancy perturbs neurodevelopmental trajectories in the offspring, including alterations in the neuroinflammatory gene expression profile and microglial number and morphology in the hippocampus, resulting in behavioural changes in adult offspring. Such early perturbations may underlie the vulnerability in human offspring for the later development of neurodevelopmental disorders, including schizophrenia. Our work highlights the importance of using live IAV in developing novel preclinical models that better recapitulate the real-world impact of inflammatory insults during pregnancy on offspring neurodevelopmental trajectories and disease susceptibility later in life.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: