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vonderEmbse et al. Neuroimmunol Neuroinflammation 2020;7:345-59 Neuroimmunology
DOI: 10.20517/2347-8659.2019.29 and Neuroinflammation

Original Article Open Access

Postnatal toxicant exposure in 3xTgAD mice
promotes gene x environment-related early

alterations to neuroimmune epigenetic profiles

Annalise N. vonderEmbse, Qing Hu, Jamie C. DeWitt

Department of Pharmacology and Toxicology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA.

Correspondence to: Dr. Annalise N. vonderEmbse, Department of Molecular Biosciences, University of California at Davis, One
Shields Ave, Davis, CA 95616, USA. E-mail: anvonderembse@ucdavis.edu
How to cite this article: vonderEmbse AN, Hu Q, DeWitt JC. Postnatal toxicant exposure in 3xTgAD mice promotes gene x
environment-related early alterations to neuroimmune epigenetic profiles. Neuroimmunol Neuroinflammation 2020;7:345-59
http://dx.doi.org/10.20517/2347-8659.2019.29

Received: 30 Dec 2019 First Decision: 26 Feb 2020 Revised: 12 Jun 2020 Accepted: 29 Jul 2020 Available online: 16 Oct 2020
Academic Editor: Athanassios P. Kyritsis Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
Aim: The purpose of this study was to evaluate sex-biased, maladaptive changes to epigenetic regulation critical
for development of neuroimmune crosstalk resulting from an early-life toxicant exposure previously associated
with increased susceptibility to later-life neurodegeneration.

Methods: An evaluation of early-life gene x environment (GxE) interactions was performed in a mouse model of
Alzheimer’s disease (Tg) orally exposed to lead acetate (Pb) from postnatal day (PND) 5-9. Following exposure,
immunohistochemical analysis was used to evaluate hippocampal expression of DAP12, a marker for perinatal
microglia related to microglial-mediated postnatal synaptic pruning of neurons. Altered profiles of three
microRNAs critical to homeostatic microglia: neuron signaling (miR-34a, miR-124, miR-132) were measured by
qRT-PCR.

Results: Atypical and deleterious expression patterns in Pb-exposed Tg mice were detected with significant female
bias by PND 10. Early exposure to Pb resulted in the upregulation of miR-124, a microRNA involved in microglial
quiescence, as well as miR-34a, involved in p53-dependent apoptosis and decreased phagocytosis, by PND 21 and
during a period of microglial-mediated synaptic pruning specific to females. In addition, we observed a sustained,
imbalanced upregulation of miR-132 in Pb-exposed Tg females as well as decreased expression of DAP12.

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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