Fitzgerald, Eamon and Sinton, Matthew C. and Wernig-Zorc, Sara and Morton, Nicholas M. and Holmes, Megan C. and Boardman, James P. and Drake, Amanda J. (2021) Altered hypothalamic DNA methylation and stress-induced hyperactivity following early life stress. EPIGENETICS & CHROMATIN, 14 (1): 31. ISSN , 1756-8935
Full text not available from this repository. (Request a copy)Abstract
Exposure to early life stress (ELS) during childhood or prenatally increases the risk of future psychiatric disorders. The effect of stress exposure during the neonatal period is less well understood. In preterm infants, exposure to invasive procedures is associated with altered brain development and future stress responses suggesting that the neonatal period could be a key time for the programming of mental health. Previous studies suggest that ELS affects the hypothalamic epigenome, making it a good candidate to mediate these effects. In this study, we used a mouse model of early life stress (modified maternal separation; MMS). We hypothesised MMS would affect the hypothalamic transcriptome and DNA methylome, and impact on adult behaviour. MMS involved repeated stimulation of pups for 1.5 h/day, whilst separated from their mother, from postnatal day (P) 4-6. 3'mRNA sequencing and DNA methylation immunoprecipitation (meDIP) sequencing were performed on hypothalamic tissue at P6. Behaviour was assessed with the elevated plus, open field mazes and in-cage monitoring at 3-4 months of age. MMS was only associated with subtle changes in gene expression, but there were widespread alterations in DNA methylation. Notably, differentially methylated regions were enriched for synapse-associated loci. MMS resulted in hyperactivity in the elevated plus and open field mazes, but in-cage monitoring revealed that this was not representative of habitual hyperactivity. ELS has marked effects on DNA methylation in the hypothalamus in early life and results in stress-specific hyperactivity in young adulthood. These results have implications for the understanding of ELS-mediated effects on brain development.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHILDHOOD MALTREATMENT; PSYCHIATRIC-DISORDERS; MATERNAL-DEPRIVATION; BRAIN-DEVELOPMENT; PROCEDURAL PAIN; PRETERM; CHILDREN; DEPRESSION; BIRTH; AGE; Early life stress; DNA methylation; Behaviour; Hypothalamus; Brain development; Preterm birth |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie III |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Sep 2022 08:04 |
| Last Modified: | 21 Sep 2022 08:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47788 |
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