Document Type

Article

Publication Date

7-2021

Identifier

DOI: 10.1159/000515750; PMCID: PMC8315678

Abstract

An adverse maternal environment (AME) predisposes adult offspring toward cognitive impairment in humans and mice. However, the underlying mechanisms remain poorly understood. Epigenetic changes in response to environmental exposure may be critical drivers of this change. Epigenetic regulators, including microRNAs, have been shown to affect cognitive function by altering hippocampal neurogenesis which is regulated in part by brain-derived neurotropic factor (BDNF). We sought to investigate the effects of AME on miR profile and their epigenetic characteristics, as well as neurogenesis and BDNF expression in mouse hippocampus. Using our mouse model of AME which is composed of maternal Western diet and prenatal environmental stress, we found that AME significantly increased hippocampal miR-10b-5p levels. We also found that AME significantly decreased DNA methylation and increased accumulations of active histone marks H3 lysine (K) 4me3, H3K14ac, and -H3K36me3 at miR-10b promoter. Furthermore, AME significantly decreased hippocampal neurogenesis by decreasing cell numbers of Ki67+ (proliferation marker), NeuroD1+ (neuronal differentiation marker), and NeuN+ (mature neuronal marker) in the dentate gyrus (DG) region concurrently with decreased hippocampal BDNF protein levels. We speculate that the changes in epigenetic profile at miR-10b promoter may contribute to upregulation of miR-10b-5p and subsequently lead to decreased BDNF levels in a model of impaired offspring hippocampal neurogenesis and cognition in mice.

Journal Title

Developmental neuroscience

Volume

43

Issue

2

First Page

95

Last Page

105

Keywords

Adverse maternal environment; Brain-derived neurotropic factor; Epigenetics; Hippocampal neurogenesis; MicroRNA-10b

Comments

This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission.

Publisher's Link: https://www.karger.com/Article/FullText/515750

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