Altered Hippocampal Epigenetic Regulation Underlying Reduced Cognitive Development in Response to Early Life Environmental Insults
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...
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doaj-fc6b86af9fd94b22a4f25f39f04185542020-11-25T01:42:27ZengMDPI AGGenes2073-44252020-02-0111216210.3390/genes11020162genes11020162Altered Hippocampal Epigenetic Regulation Underlying Reduced Cognitive Development in Response to Early Life Environmental InsultsKyle M. Schachtschneider0Michael E. Welge1Loretta S. Auvil2Sulalita Chaki3Laurie A. Rund4Ole Madsen5Monica R.P. Elmore6Rodney W. Johnson7Martien A.M. Groenen8Lawrence B. Schook9Department of Radiology, University of Illinois at Chicago, Chicago, IL 60607, USANational Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USANational Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USADepartment of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 616280, USADepartment of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 616280, USAAnimal Breeding and Genomics, Wageningen University, 6708 Wageningen, The NetherlandsDepartment of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 616280, USADepartment of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 616280, USAAnimal Breeding and Genomics, Wageningen University, 6708 Wageningen, The NetherlandsDepartment of Radiology, University of Illinois at Chicago, Chicago, IL 60607, USAThe 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, <i>VWF </i>and <i>LRRC32</i>, 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.https://www.mdpi.com/2073-4425/11/2/162porcine biomedical modelshippocampuscognitive developmentdna methylationrna-seqmachine learning |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kyle M. Schachtschneider Michael E. Welge Loretta S. Auvil Sulalita Chaki Laurie A. Rund Ole Madsen Monica R.P. Elmore Rodney W. Johnson Martien A.M. Groenen Lawrence B. Schook |
spellingShingle |
Kyle M. Schachtschneider Michael E. Welge Loretta S. Auvil Sulalita Chaki Laurie A. Rund Ole Madsen Monica R.P. Elmore Rodney W. Johnson Martien A.M. Groenen Lawrence B. Schook Altered Hippocampal Epigenetic Regulation Underlying Reduced Cognitive Development in Response to Early Life Environmental Insults Genes porcine biomedical models hippocampus cognitive development dna methylation rna-seq machine learning |
author_facet |
Kyle M. Schachtschneider Michael E. Welge Loretta S. Auvil Sulalita Chaki Laurie A. Rund Ole Madsen Monica R.P. Elmore Rodney W. Johnson Martien A.M. Groenen Lawrence B. Schook |
author_sort |
Kyle M. Schachtschneider |
title |
Altered Hippocampal Epigenetic Regulation Underlying Reduced Cognitive Development in Response to Early Life Environmental Insults |
title_short |
Altered Hippocampal Epigenetic Regulation Underlying Reduced Cognitive Development in Response to Early Life Environmental Insults |
title_full |
Altered Hippocampal Epigenetic Regulation Underlying Reduced Cognitive Development in Response to Early Life Environmental Insults |
title_fullStr |
Altered Hippocampal Epigenetic Regulation Underlying Reduced Cognitive Development in Response to Early Life Environmental Insults |
title_full_unstemmed |
Altered Hippocampal Epigenetic Regulation Underlying Reduced Cognitive Development in Response to Early Life Environmental Insults |
title_sort |
altered hippocampal epigenetic regulation underlying reduced cognitive development in response to early life environmental insults |
publisher |
MDPI AG |
series |
Genes |
issn |
2073-4425 |
publishDate |
2020-02-01 |
description |
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, <i>VWF </i>and <i>LRRC32</i>, 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. |
topic |
porcine biomedical models hippocampus cognitive development dna methylation rna-seq machine learning |
url |
https://www.mdpi.com/2073-4425/11/2/162 |
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