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Open AccessArticle

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

1
Department of Radiology, University of Illinois at Chicago, Chicago, IL 60607, USA
2
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA
3
National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USA
4
Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 616280, USA
5
Animal Breeding and Genomics, Wageningen University, 6708 Wageningen, The Netherlands
*
Author to whom correspondence should be addressed.
Genes 2020, 11(2), 162; https://doi.org/10.3390/genes11020162
Received: 13 December 2019 / Revised: 30 January 2020 / Accepted: 1 February 2020 / Published: 4 February 2020
(This article belongs to the Special Issue Next Gen Porcine Genetics and Genomics: Implications for Health)
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. View Full-Text
Keywords: porcine biomedical models; hippocampus; cognitive development; DNA methylation; RNA-seq; machine learning porcine biomedical models; hippocampus; cognitive development; DNA methylation; RNA-seq; machine learning
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Schachtschneider, K.M.; Welge, M.E.; Auvil, L.S.; Chaki, S.; Rund, L.A.; Madsen, O.; Elmore, M.R.; Johnson, R.W.; Groenen, M.A.; Schook, L.B. Altered Hippocampal Epigenetic Regulation Underlying Reduced Cognitive Development in Response to Early Life Environmental Insults. Genes 2020, 11, 162.

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