Microglia from offspring of dams with allergic asthma exhibit epigenomic alterations in genes dysregulated in autism

Details

• Alternative Title:
  Glia
• Personal Author:
  Ciernia, Annie Vogel ; Careaga, Milo ; Ashwood, Paul ; LaSalle, Janine
• Description:
  Dysregulation in immune responses during pregnancy increases the risk of a having a child with an autism spectrum disorder (ASD). Asthma is one of the most common chronic diseases among pregnant women, and symptoms often worsen during pregnancy. We recently developed a mouse model of maternal allergic asthma (MAA) that induces changes in sociability, repetitive, and perseverative behaviors in the offspring. Since epigenetic changes help a static genome adapt to the maternal environment, activation of the immune system may epigenetically alter fetal microglia, the brain's resident immune cells. We therefore tested the hypothesis that epigenomic alterations to microglia may be involved in behavioral abnormalities observed in MAA offspring. We used the genome-wide approaches of whole genome bisulfite sequencing to examine DNA methylation and RNA sequencing to examine gene expression in microglia from juvenile MAA offspring. Differentially methylated regions were enriched for immune signaling pathways and important microglial developmental transcription factor binding motifs. Differential expression analysis identified genes involved in controlling microglial sensitivity to the environment and shaping neuronal connections in the developing brain. Differentially expressed genes significantly overlapped genes with altered expression in human ASD cortex, supporting a role for microglia in the pathogenesis of ASD.
• Subjects:
  Animals Article Asthma Autism Spectrum Disorders Autistic Disorder Disease Models, Animal DNA Methylation Epigenesis, Genetic Female Gene Expression Hypersensitivity Maternal Allergic Asthma Maternal Immune Activation Mice, Inbred C57BL Microglia Pregnancy Prenatal Exposure Delayed Effects Random Allocation Sequence Analysis, RNA Transcriptome Whole Genome Sequencing

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• Source:
  Glia. 66(3):505-521
• Pubmed ID:
  29134693
• Pubmed Central ID:
  PMC5767155
• Document Type:
  Journal Article
• Funding:
  P30 CA093373/NCI NIH HHS/National Cancer Institute/United States ; T32 MH073124/NIMH NIH HHS/National Institute of Mental Health/United States ; S10 RR026825/NCRR NIH HHS/National Center for Research Resources/United States ; U54 HD079125/NICHD NIH HHS/National Institute of Child Health & Human Development/United States ; R21 HD086669/NICHD NIH HHS/National Institute of Child Health & Human Development/United States ; R01 HD041462/NICHD NIH HHS/National Institute of Child Health & Human Development/United States ; R21 ES025560/NIEHS NIH HHS/National Institute of Environmental Health Sciences/United States ; R21 MH116383/NIMH NIH HHS/National Institute of Mental Health/United States ; S10 OD018174/ODCDC CDC HHS/Office of the Director/United States ; R01 NS081913/NINDS NIH HHS/National Institute of Neurological Disorders and Stroke/United States ; C06 RR012088/NCRR NIH HHS/National Center for Research Resources/United States
• Volume:
  66
• Issue:
  3
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:a3073684d5ad586ab27b3dded6faa06d9a67f690b3999e11e35a39dbad953cc2
• Download URL:
  https://stacks.cdc.gov/view/cdc/80485/cdc_80485_DS1.pdf
• File Type:
  [PDF - 984.61 KB ]