9
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Sex- and brain region- specific effects of prenatal stress and lead exposure on permissive and repressive post-translational histone modifications from embryonic development through adulthood

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Developmental exposure to prenatal stress (PS) and lead (Pb) can affect brain development and adversely influence behavior and cognition. Epigenetic-based gene regulation is crucial for normal brain development and mis-regulation, in any form, can result in neurodevelopmental disorders. Post-translational histone modifications (PTHMs) are an integral and dynamic component of the epigenetic machinery involved in gene regulation. Exposures to Pb and/or PS may alter PTHM profiles, promoting lifelong alterations in brain function observed following Pb ± PS exposure. Here we examined the effects of Pb ± PS on global levels of activating marks H3K9Ac and H3K4Me3 and repressive marks H3K9Me2 and H3K27Me3 at different developmental stages: E18, PND0, PND6 and PND60. Dams were exposed to 0 or 100 ppm Pb beginning 2 months prior to breeding followed by no PS (NS) or PS resulting in 4 offspring treatment groups per sex: 0-NS (control), 0-PS, 100-NS and 100-PS. Global levels of PTHMs varied from E18 through adulthood even in control mice, and were influenced by sex and brain-region. The developmental trajectory of these PTHM levels was further modified by Pb ± PS in a sex-, brain region-and age-dependent manner. Females showed a preferential response to Pb alone in frontal cortex (FC) and differentially to PS alone and combined Pb + PS in hippocampus (HIPP). In males, PS-induced increases in PTHM levels in FC, whereas PS produced reductions in HIPP. Pb ± PS-based changes in PTHM levels continued to be observed in adulthood (PND60), demonstrating the la sting effect of these early life environmental events on these histone marks. These results indicate that epigenetic consequences of Pb ± PS and their contribution to mechanisms of toxicity are sex dependent. Additional studies will assist in understanding the functional significance of these changes in PTHM levels on expression of individual genes, functional pathways, and ultimately, their behavioral consequences.

          Related collections

          Author and article information

          Journal
          7905589
          6173
          Neurotoxicology
          Neurotoxicology
          Neurotoxicology
          0161-813X
          1872-9711
          31 July 2017
          13 July 2017
          September 2017
          01 September 2018
          : 62
          : 207-217
          Affiliations
          [a ]Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, United States
          [b ]Department of Environmental Medicine, University of Rochester Medical Center, Rochester NY, United States
          Author notes
          [* ]Corresponding author at: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, JAH 521, Philadelphia, PA, United States. jay.schneider@ 123456jefferson.edu (J.S. Schneider)
          Article
          PMC5623619 PMC5623619 5623619 nihpa896187
          10.1016/j.neuro.2017.07.002
          5623619
          28712943
          Categories
          Article

          Comments

          Comment on this article