Altered Hippocampal Epigenetic Regulation Underlying Reduced Cognitive Development in Response to Early Life Environmental Insults.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101551097 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4425 (Electronic) Linking ISSN: 20734425 NLM ISO Abbreviation: Genes (Basel) Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel : MDPI
    • Subject Terms:
      DNA Methylation* ; Epigenesis, Genetic*; Biomarkers/*analysis ; Cognition Disorders/*etiology ; Environmental Exposure/*adverse effects ; Hippocampus/*pathology; Animals ; Animals, Newborn ; Cell Differentiation ; Cognition Disorders/metabolism ; Cognition Disorders/pathology ; CpG Islands ; Female ; Hippocampus/metabolism ; Swine
    • Abstract:
      The hippocampus is involved in learning and memory and undergoes significant growth and maturation during the neonatal period. Environmental insults during this developmental timeframe can have lasting effects on brain structure and function. This study assessed hippocampal DNA methylation and gene transcription from two independent studies reporting reduced cognitive development stemming from early life environmental insults (iron deficiency and porcine reproductive and respiratory syndrome virus (PRRSv) infection) using porcine biomedical models. In total, 420 differentially expressed genes (DEGs) were identified between the reduced cognition and control groups, including genes involved in neurodevelopment and function. Gene ontology (GO) terms enriched for DEGs were associated with immune responses, angiogenesis, and cellular development. In addition, 116 differentially methylated regions (DMRs) were identified, which overlapped 125 genes. While no GO terms were enriched for genes overlapping DMRs, many of these genes are known to be involved in neurodevelopment and function, angiogenesis, and immunity. The observed altered methylation and expression of genes involved in neurological function suggest reduced cognition in response to early life environmental insults is due to altered cholinergic signaling and calcium regulation. Finally, two DMRs overlapped with two DEGs, VWF and LRRC32 , which are associated with blood brain barrier permeability and regulatory T-cell activation, respectively. These results support the role of altered hippocampal DNA methylation and gene expression in early life environmentally-induced reductions in cognitive development across independent studies.
      Competing Interests: The authors declare no conflict of interest.
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    • Grant Information:
      R01 HD069899 United States HD NICHD NIH HHS
    • Contributed Indexing:
      Keywords: DNA methylation; RNA-seq; cognitive development; hippocampus; machine learning; porcine biomedical models
    • Accession Number:
      0 (Biomarkers)
    • Publication Date:
      Date Created: 20200209 Date Completed: 20201201 Latest Revision: 20201201
    • Publication Date:
      20221213
    • Accession Number:
      PMC7074491
    • Accession Number:
      10.3390/genes11020162
    • Accession Number:
      32033187