scholarly journals 138 Prenatal stress alters genes in signaling pathways influencing behavior and stress response by differential methylation of DNA.

2018 ◽  
Vol 96 (suppl_3) ◽  
pp. 349-350
Author(s):  
B Littlejohn ◽  
D Price ◽  
D Neuendorff ◽  
J Carroll ◽  
R Vann ◽  
...  
Keyword(s):  
Stress Response ◽  
Signaling Pathways ◽  
Prenatal Stress ◽  
Differential Methylation ◽  
Methylation Of Dna

scholarly journals Influence of prenatal transportation stress-induced differential DNA methylation on the physiological control of behavior and stress response in suckling Brahman bull calves

2019 ◽  
Vol 98 (1) ◽  
Author(s):  
Brittni P Littlejohn ◽  
Deborah M Price ◽  
Don A Neuendorff ◽  
Jeffery A Carroll ◽  
Rhonda C Vann ◽  
...  
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
White Blood Cells ◽  
Differential Methylation ◽  
Receptor Signaling ◽  
Promoter Regions ◽  
Methylation Of Dna ◽  
Bull Calves ◽  
Differentially Methylated Genes ◽  
Canonical Pathways

Abstract The objective of this experiment was to examine potential differential methylation of DNA as a mechanism for altered behavioral and stress responses in prenatally stressed (PNS) compared with nonprenatally stressed (Control) young bull calves. Mature Brahman cows (n = 48) were transported for 2-h periods at 60 ± 5, 80 ± 5, 100 ± 5, 120 ± 5, and 140 ± 5 d of gestation (Transported group) or maintained as nontransported Controls (n = 48). From the offspring born to Transported and Control cows, a subset of 28-d-old intact bulls (n = 7 PNS; n = 7 Control) were evaluated for methylation of DNA of behavior and stress response–associated genes. Methylation of DNA from white blood cells was assessed via reduced representation bisulfite sequencing methods. Because increased methylation of DNA within gene promoter regions has been associated with decreased transcriptional activity of the corresponding gene, differentially methylated (P ≤ 0.05) CG sites (cytosine followed by a guanine nucleotide) located within promoter regions (n = 1,205) were used to predict (using Ingenuity Pathway Analysis software) alterations to canonical pathways in PNS compared with Control bull calves. Among differentially methylated genes (P ≤ 0.05) related to behavior and the stress response were OPRK1, OPRM1, PENK, POMC, NR3C2, TH, DRD1, DRD5, COMT, HTR6, HTR5A, GABRA4, GABRQ, and GAD2. Among altered (P < 0.05) signaling pathways related to behavior and the stress response were Opioid Signaling, Corticotropin-Releasing Hormone Signaling, Dopamine Receptor Signaling, Dopamine-DARPP32 Feedback in cAMP Signaling, Serotonin Receptor Signaling, and GABA Receptor Signaling. Alterations to behavior and stress response–related genes and canonical pathways supported previously observed elevations in temperament score and serum cortisol through weaning in the larger population of PNS calves from which bulls in this study were derived. Differential methylation of DNA and predicted alterations to behavior and stress response–related pathways in PNS compared with Control bull calves suggest epigenetic programming of behavior and the stress response in utero.

scholarly journals 376 Awardee Talk - Prenatal transportation stress alters physiology of suckling Brahman calves as mediated by changes in DNA methylation

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 142-142
Author(s):  
Brittni P Littlejohn ◽  
Debbi M Price ◽  
Don A Neuendorff ◽  
Jeffery A Carroll ◽  
Rhonda C Vann ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stress Response ◽  
Animal Health ◽  
White Blood Cells ◽  
Insulin Response ◽  
Differential Methylation ◽  
Developmental Trajectory ◽  
Prenatal Programming ◽  
Methylation Of Dna ◽  
And Control

Abstract Mechanisms by which prenatal programming alters the developmental trajectory of biological systems in utero is of relevance to animal agriculture. We hypothesized that prenatally stressed (PNS) calves would exhibit altered postnatal phenotype and differential methylation of DNA. Mature Brahman cows (n = 48) were transported for 2-h periods at 60, 80, 100, 120, and 140 (± 5) d of gestation or maintained as non-transported Controls (n = 48). PNS calves exhibited more excitable temperaments and increased circulating concentrations of cortisol. In response to a glucose tolerance test administered to a subset of PNS and Control bulls, PNS calves returned to basal concentrations of insulin more rapidly and exhibited a lower total area under the insulin response curve. In response to a lipopolysaccharide challenge administered to a subset of PNS and Control bulls, PNS calves exhibited greater circulating concentrations of cortisol and a greater change from baseline for IFN-γ and monocytes. Reduced representation bisulfite sequencing was used to assess methylation of DNA from white blood cells in a subset of 28-d-old bull calves. Because increased methylation of DNA in a gene promoter region typically results in decreased transcriptional activity, differentially methylated CG sites located within promoter regions (n = 1,205) were used to predict alterations to canonical pathways using Ingenuity Pathway Analysis software. There were 113 pathways altered (P ≤ 0.05) in PNS calves. Among these were pathways related to behavior, stress response, metabolism, and immune function. In support of our hypotheses, differential methylation in gene regions related to temperament, stress response, metabolism, and immune response corresponded to phenotypic differences observed in PNS calves, suggesting DNA methylation as a mechanistic basis for prenatal programming. The role of the prenatal epigenome in shaping postnatal outcomes provides novel opportunities to improve animal health and production traits.

scholarly journals Integrated Stress Response Signaling Pathways Induced by Supraphysiological Concentrations of Thyroid Hormone Inhibit Viral Replication

2016 ◽  
Vol 5 ◽  
pp. STI.S39844 ◽  
Author(s):  
Mohammad Ishaq ◽  
Ven Natarajan
Keyword(s):  
Stress Response ◽  
Signaling Pathways ◽  
Antiviral Agents ◽  
Integrated Stress Response ◽  
Dependent Protein Kinase ◽  
Antiviral Responses ◽  
Stress Markers ◽  
Signaling Mechanisms ◽  
Dependent Protein ◽  
Vesicular Stomatitis

Supraphysiological concentrations (SPCs) of triiodo-L-thyronine (T3) have been used in the treatment of a number of nonviral diseases. However, the signaling mechanisms that regulate the function of T3 at these concentrations and their role in modulating cellular stress pathways and antiviral responses are unknown. Here, we have investigated the effects of SPCs of T3 on integrated stress response (ISR) signaling pathways and the replication of vesicular stomatitis virus (VSV). T3 amplified Poly IC-induced activation of RNA-dependent protein kinase, induced phosphorylation of eIF2α, stress granule (SG) formation, IRE1α phosphorylation, XBP1 splicing, and the expression of stress markers. T3 inhibited VSV replication by modulating SG formation and the expression of stress response markers. ISR activator guanabenz also inhibited VSV replication and amplified T3-induced anti-VSV response. To summarize, we have uncovered novel functions of T3 at SPCs as an activator of ISR signaling pathways and an inhibitor of VSV replication. This study offers a proof of principle of the concept that ISR activating agents like SPC of T3 and guanabenz can be potential antiviral agents.

scholarly journals The unpredictability of prolonged activation of stress response pathways

2015 ◽  
Vol 209 (6) ◽  
pp. 781-787 ◽  
Author(s):  
Lilian T. Lamech ◽  
Cole M. Haynes
Keyword(s):  
Stress Response ◽  
Signaling Pathways ◽  
Stress Responses ◽  
Degenerative Diseases ◽  
Response To Stress ◽  
Cellular Compartments

In response to stress, cellular compartments activate signaling pathways that mediate transcriptional programs to promote survival and reestablish homeostasis. Manipulation of the magnitude and duration of the activation of stress responses has been proposed as a strategy to prevent or repair the damage associated with aging or degenerative diseases. However, as these pathways likely evolved to respond specifically to transient perturbations, the unpredictability of prolonged activation should be considered.

Factors Affecting Differential Methylation of DNA Promoters in Arsenic-Exposed Populations

2018 ◽  
Vol 189 (2) ◽  
pp. 437-446 ◽  
Author(s):  
Yanting Zhang ◽  
Yuanyuan Li ◽  
Lanrong Luo ◽  
Qian He ◽  
Yanhui Gao ◽  
...  
Keyword(s):  
Differential Methylation ◽  
Factors Affecting ◽  
Methylation Of Dna ◽  
Dna Promoters
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