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Alteration of the brain methylation landscape following postnatal inflammatory injury in rat pups
Author(s) -
Pierre Wyston C.,
Legault LisaMarie,
Londono Irene,
McGraw Serge,
Lodygensky Gregory A.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201901461r
Subject(s) - epigenetics , dna methylation , methylation , corpus callosum , biology , bisulfite , lipopolysaccharide , gene , differentially methylated regions , inflammation , genetics , immunology , neuroscience , gene expression
Abstract Preterm infants are vulnerable to inflammation‐induced white matter injury (WMI), which is associated with neurocognitive impairment and increased risk of neuropsychiatric diseases in adulthood. Epigenetic mechanisms, particularly DNA methylation, play a role in normal development and modulate the response to pathological challenges. Our aims were to determine how WMI triggered DNA methylation alterations in brains of neonatal rats and if such changes persisted over time. We used a robust model of WMI by injecting lipopolysaccharide (LPS) or sterile saline in the corpus callosum of 3‐day‐old (P3) rat pups. Brains were collected 24 hours (P4) and 21 days post‐injection (P24). We extracted genomic DNA from the brain to establish genome‐wide quantitative DNA methylation profiles using reduced representation bisulfite sequencing. Neonatal LPS exposure induced a persistent increased methylation of genes related to nervous system development and a reduced methylation of genes associated with inflammatory pathways. These findings suggest that early‐life neuroinflammatory exposure impacts the cerebral methylation landscape with determining widespread epigenetic modifications especially in genes related to neurodevelopment.