Altered hippocampal epigenetic regulation underlying reduced cognitive development in response to early life environmental insults

K.M. Schachtschneider, M.E. Welge, L.S. Auvil, S. Chaki, L.A. Rund, O. Madsen, M.R.P. Elmore, Rodney W. Johnson, M. Groenen, Lawrence B. Schook

Research output: Chapter in Book/Report/Conference proceedingAbstract

Abstract

The hippocampus is involved in learning and memory and undergoes significant growth and maturation during the neonatal period. Environmental insults during this developmental period can affect epigenetic patterns and have lasting effects on brain structure and function. This study assessed hippocampal DNA methylation (reduced representation bisulfite sequencing) and gene transcription (RNA-seq) from 2 independent studies reporting reduced cognitive development stemming from early life environmental insults (iron deficiency and PRRSv infection) using porcine biomedical models. The Boruta machine learning approach was utilized to identify DNA methylation and gene expression features attributed to the reduced cognition phenotype. In total, 1,743 differentially expressed genes (DEGs) were identified between the reduced cognition and control groups, with samples clustering by group when comparing expression of the identified DEGs (ANOSIM R = 0.68, p-value = 0.001). GO term enrichment analysis resulted in the identification of 219 GO terms enriched for DEGs, including terms associated with immune responses, angiogenesis, cellular signaling, development, differentiation, and proliferation. In addition, 943 differentially methylated CpG regions (DMRs) were identified between the reduced cognition and control groups. While samples did not cluster by group when comparing methylation levels of the 30,696 tested regions (ANOSIM R = −0.07, p-value = 0.731), samples clustered by group when comparing expression levels of the 943 DMRs (ANOSIM R =0.92, p-value = 0.001). These 943 DMRs overlapped with 891 gene regions. Overlapping genes were enriched for 171 GO terms, including terms associated with neurodevelopment, cellular signaling, development, differentiation, and proliferation. Finally, the identified DMRs overlapped with 67 DEGs, including 18 genes involved in neurodevelopment, function, and maintenance of the blood brain barrier. Together, these results support the role of altered hippocampal DNA methylation and gene expression in early life environmentally induced reductions in cognitive development across 2 independent studies.
Original languageEnglish
Title of host publicationISAG 2019 Abstract Book
Subtitle of host publication37th International Society for Animal Genetics Conference, July 7-12, 2019 - Lleida, Spain
Pages158-158
Publication statusPublished - 7 Jul 2019
Event37th International Society for Animal Genetics Conference (ISAG) - Lleida, Spain
Duration: 7 Jul 201912 Jul 2019

Conference

Conference37th International Society for Animal Genetics Conference (ISAG)
CountrySpain
CityLleida
Period7/07/1912/07/19

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Epigenomics
DNA Methylation
Cognition
Genes
Overlapping Genes
vpr Genes
Gene Expression
Control Groups
Blood-Brain Barrier
Cellular Immunity
Methylation
Cluster Analysis
Hippocampus
Swine
Iron
Maintenance
Learning
RNA
Phenotype
Brain

Cite this

Schachtschneider, K. M., Welge, M. E., Auvil, L. S., Chaki, S., Rund, L. A., Madsen, O., ... Schook, L. B. (2019). Altered hippocampal epigenetic regulation underlying reduced cognitive development in response to early life environmental insults. In ISAG 2019 Abstract Book: 37th International Society for Animal Genetics Conference, July 7-12, 2019 - Lleida, Spain (pp. 158-158)
Schachtschneider, K.M. ; Welge, M.E. ; Auvil, L.S. ; Chaki, S. ; Rund, L.A. ; Madsen, O. ; Elmore, M.R.P. ; Johnson, Rodney W. ; Groenen, M. ; Schook, Lawrence B. / Altered hippocampal epigenetic regulation underlying reduced cognitive development in response to early life environmental insults. ISAG 2019 Abstract Book: 37th International Society for Animal Genetics Conference, July 7-12, 2019 - Lleida, Spain. 2019. pp. 158-158
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title = "Altered hippocampal epigenetic regulation underlying reduced cognitive development in response to early life environmental insults",
abstract = "The hippocampus is involved in learning and memory and undergoes significant growth and maturation during the neonatal period. Environmental insults during this developmental period can affect epigenetic patterns and have lasting effects on brain structure and function. This study assessed hippocampal DNA methylation (reduced representation bisulfite sequencing) and gene transcription (RNA-seq) from 2 independent studies reporting reduced cognitive development stemming from early life environmental insults (iron deficiency and PRRSv infection) using porcine biomedical models. The Boruta machine learning approach was utilized to identify DNA methylation and gene expression features attributed to the reduced cognition phenotype. In total, 1,743 differentially expressed genes (DEGs) were identified between the reduced cognition and control groups, with samples clustering by group when comparing expression of the identified DEGs (ANOSIM R = 0.68, p-value = 0.001). GO term enrichment analysis resulted in the identification of 219 GO terms enriched for DEGs, including terms associated with immune responses, angiogenesis, cellular signaling, development, differentiation, and proliferation. In addition, 943 differentially methylated CpG regions (DMRs) were identified between the reduced cognition and control groups. While samples did not cluster by group when comparing methylation levels of the 30,696 tested regions (ANOSIM R = −0.07, p-value = 0.731), samples clustered by group when comparing expression levels of the 943 DMRs (ANOSIM R =0.92, p-value = 0.001). These 943 DMRs overlapped with 891 gene regions. Overlapping genes were enriched for 171 GO terms, including terms associated with neurodevelopment, cellular signaling, development, differentiation, and proliferation. Finally, the identified DMRs overlapped with 67 DEGs, including 18 genes involved in neurodevelopment, function, and maintenance of the blood brain barrier. Together, these results support the role of altered hippocampal DNA methylation and gene expression in early life environmentally induced reductions in cognitive development across 2 independent studies.",
author = "K.M. Schachtschneider and M.E. Welge and L.S. Auvil and S. Chaki and L.A. Rund and O. Madsen and M.R.P. Elmore and Johnson, {Rodney W.} and M. Groenen and Schook, {Lawrence B.}",
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Schachtschneider, KM, Welge, ME, Auvil, LS, Chaki, S, Rund, LA, Madsen, O, Elmore, MRP, Johnson, RW, Groenen, M & Schook, LB 2019, Altered hippocampal epigenetic regulation underlying reduced cognitive development in response to early life environmental insults. in ISAG 2019 Abstract Book: 37th International Society for Animal Genetics Conference, July 7-12, 2019 - Lleida, Spain. pp. 158-158, Lleida, Spain, 7/07/19.

Altered hippocampal epigenetic regulation underlying reduced cognitive development in response to early life environmental insults. / Schachtschneider, K.M.; Welge, M.E.; Auvil, L.S.; Chaki, S.; Rund, L.A.; Madsen, O.; Elmore, M.R.P.; Johnson, Rodney W.; Groenen, M.; Schook, Lawrence B.

ISAG 2019 Abstract Book: 37th International Society for Animal Genetics Conference, July 7-12, 2019 - Lleida, Spain. 2019. p. 158-158.

Research output: Chapter in Book/Report/Conference proceedingAbstract

TY - CHAP

T1 - Altered hippocampal epigenetic regulation underlying reduced cognitive development in response to early life environmental insults

AU - Schachtschneider, K.M.

AU - Welge, M.E.

AU - Auvil, L.S.

AU - Chaki, S.

AU - Rund, L.A.

AU - Madsen, O.

AU - Elmore, M.R.P.

AU - Johnson, Rodney W.

AU - Groenen, M.

AU - Schook, Lawrence B.

N1 - Poster

PY - 2019/7/7

Y1 - 2019/7/7

N2 - The hippocampus is involved in learning and memory and undergoes significant growth and maturation during the neonatal period. Environmental insults during this developmental period can affect epigenetic patterns and have lasting effects on brain structure and function. This study assessed hippocampal DNA methylation (reduced representation bisulfite sequencing) and gene transcription (RNA-seq) from 2 independent studies reporting reduced cognitive development stemming from early life environmental insults (iron deficiency and PRRSv infection) using porcine biomedical models. The Boruta machine learning approach was utilized to identify DNA methylation and gene expression features attributed to the reduced cognition phenotype. In total, 1,743 differentially expressed genes (DEGs) were identified between the reduced cognition and control groups, with samples clustering by group when comparing expression of the identified DEGs (ANOSIM R = 0.68, p-value = 0.001). GO term enrichment analysis resulted in the identification of 219 GO terms enriched for DEGs, including terms associated with immune responses, angiogenesis, cellular signaling, development, differentiation, and proliferation. In addition, 943 differentially methylated CpG regions (DMRs) were identified between the reduced cognition and control groups. While samples did not cluster by group when comparing methylation levels of the 30,696 tested regions (ANOSIM R = −0.07, p-value = 0.731), samples clustered by group when comparing expression levels of the 943 DMRs (ANOSIM R =0.92, p-value = 0.001). These 943 DMRs overlapped with 891 gene regions. Overlapping genes were enriched for 171 GO terms, including terms associated with neurodevelopment, cellular signaling, development, differentiation, and proliferation. Finally, the identified DMRs overlapped with 67 DEGs, including 18 genes involved in neurodevelopment, function, and maintenance of the blood brain barrier. Together, these results support the role of altered hippocampal DNA methylation and gene expression in early life environmentally induced reductions in cognitive development across 2 independent studies.

AB - The hippocampus is involved in learning and memory and undergoes significant growth and maturation during the neonatal period. Environmental insults during this developmental period can affect epigenetic patterns and have lasting effects on brain structure and function. This study assessed hippocampal DNA methylation (reduced representation bisulfite sequencing) and gene transcription (RNA-seq) from 2 independent studies reporting reduced cognitive development stemming from early life environmental insults (iron deficiency and PRRSv infection) using porcine biomedical models. The Boruta machine learning approach was utilized to identify DNA methylation and gene expression features attributed to the reduced cognition phenotype. In total, 1,743 differentially expressed genes (DEGs) were identified between the reduced cognition and control groups, with samples clustering by group when comparing expression of the identified DEGs (ANOSIM R = 0.68, p-value = 0.001). GO term enrichment analysis resulted in the identification of 219 GO terms enriched for DEGs, including terms associated with immune responses, angiogenesis, cellular signaling, development, differentiation, and proliferation. In addition, 943 differentially methylated CpG regions (DMRs) were identified between the reduced cognition and control groups. While samples did not cluster by group when comparing methylation levels of the 30,696 tested regions (ANOSIM R = −0.07, p-value = 0.731), samples clustered by group when comparing expression levels of the 943 DMRs (ANOSIM R =0.92, p-value = 0.001). These 943 DMRs overlapped with 891 gene regions. Overlapping genes were enriched for 171 GO terms, including terms associated with neurodevelopment, cellular signaling, development, differentiation, and proliferation. Finally, the identified DMRs overlapped with 67 DEGs, including 18 genes involved in neurodevelopment, function, and maintenance of the blood brain barrier. Together, these results support the role of altered hippocampal DNA methylation and gene expression in early life environmentally induced reductions in cognitive development across 2 independent studies.

M3 - Abstract

SP - 158

EP - 158

BT - ISAG 2019 Abstract Book

ER -

Schachtschneider KM, Welge ME, Auvil LS, Chaki S, Rund LA, Madsen O et al. Altered hippocampal epigenetic regulation underlying reduced cognitive development in response to early life environmental insults. In ISAG 2019 Abstract Book: 37th International Society for Animal Genetics Conference, July 7-12, 2019 - Lleida, Spain. 2019. p. 158-158