Prenatally traumatized mice reveal hippocampal methylation and expression changes of the stress-related genes Crhr1 and Fkbp5

Language
en
Document Type
Article
Issue Date
2023-03-28
First published
2021-03-23
Issue Year
2021
Authors
Plank, Anne-Christine
Frey, Stefan
Basedow, Lukas Andreas
Solati, Jalal
Canneva, Fabio
Hörsten, Stephan von
Kratz, Oliver
Moll, Gunther H.
Golub, Yulia
Editor
Publisher
Nature Publishing Group UK
Abstract

In our previous study, we found that prenatal trauma exposure leads to an anxiety phenotype in mouse pups, characterized by increased corticosterone levels and increased anxiety-like behavior. In order to understand the mechanisms by which aversive in utero experience leads to these long-lasting behavioral and neuroendocrine changes, we investigated stress reactivity of prenatally traumatized (PT) mice, as well as the expression and methylation levels of several key regulatory genes of the stress axis in the dorsal hippocampus (dHPC) of the PT embryo and adult mice. We detected increased corticotropin-releasing hormone receptor 1 (Crhr1) and decreased FK506 binding protein 5 (Fkbp5) mRNA levels in the left dHPC of adult PT mice. These alterations were accompanied by a decreased methylation status of the Crhr1 promoter and an increased methylation status of the Fkbp5 promoter, respectively. Interestingly, the changes in Fkbp5 and Crhr1 mRNA levels were not detected in the embryonic dHPC of PT mice. Together, our findings provide evidence that prenatal trauma has a long-term impact on stress axis function and anxiety phenotype associated with altered Crhr1 and Fkbp5 transcripts and promoter methylation.

Journal Title
Translational Psychiatry
Volume
11
Issue
1
Citation

Translational Psychiatry 11 (2021), 183. https://www.nature.com/articles/s41398-021-01293-y