Maternal behaviours and adult offspring behavioural deficits are predicted by maternal TNFα concentration in a rat model of neurodevelopmental disorders.

Autor: Potter HG; Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, United Kingdom; School of Medicine, University of Central Lancashire, Burnley BB11 1RA, United Kingdom. Electronic address: HPotter@uclan.ac.uk., Kowash HM; Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, St Mary's Hospital, Manchester M13 9WL, United Kingdom., Woods RM; Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, United Kingdom., Revill G; Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, United Kingdom., Grime A; Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, United Kingdom., Deeney B; Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, United Kingdom., Burgess MA; Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, United Kingdom., Aarons T; Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, United Kingdom., Glazier JD; Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, United Kingdom., Neill JC; Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, United Kingdom; Chair of Medical Psychedelics Working Group, Drug Science, United Kingdom., Hager R; Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, United Kingdom.
Jazyk: angličtina
Zdroj: Brain, behavior, and immunity [Brain Behav Immun] 2023 Feb; Vol. 108, pp. 162-175. Date of Electronic Publication: 2022 Dec 08.
DOI: 10.1016/j.bbi.2022.12.003
Abstrakt: Exposure to inflammatory stressors during fetal development is a major risk factor for neurodevelopmental disorders (NDDs) in adult offspring. Maternal immune activation (MIA), induced by infection, causes an acute increase in pro-inflammatory cytokines which can increase the risk for NDDs directly by inducing placental and fetal brain inflammation, or indirectly through affecting maternal care behaviours thereby affecting postnatal brain development. Which of these two potential mechanisms dominates in increasing offspring risk for NDDs remains unclear. Here, we show that acute systemic maternal inflammation induced by the viral mimetic polyinosinic:polycytidylic acid (poly I:C) on gestational day 15 of rat pregnancy affects offspring and maternal behaviour, offspring cognition, and expression of NDD-relevant genes in the offspring brain. Dams exposed to poly I:C elicited an acute increase in the pro-inflammatory cytokine tumour necrosis factor (TNF; referred to here as TNFα), which predicted disruption of key maternal care behaviours. Offspring of poly I:C-treated dams showed early behavioural and adult cognitive deficits correlated to the maternal TNFα response, but, importantly, not with altered maternal care. We also found interacting effects of sex and treatment on GABAergic gene expression and DNA methylation in these offspring in a brain region-specific manner, including increased parvalbumin expression in the female adolescent frontal cortex. We conclude that the MIA-induced elevation of TNFα in the maternal compartment affects fetal neurodevelopment leading to altered offspring behaviour and cognition. Our results suggest that a focus on prenatal pathways affecting fetal neurodevelopment would provide greater insights into the mechanisms underpinning the TNFα-mediated genesis of altered offspring behaviour and cognition following maternal inflammation.
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 © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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