Research Information System
FENS Forum 2022, Paris, France, 9 - 13 July 2022, pp.1553
Early life stress (ELS) can induce
epigenetically mediated long-lasting changes of gene expression, which may
underlie altered responses towards stress at adulthood. The Neuropeptide Y system
is involved the regulation of stress response throughout development via its
receptors, specifically the activation of NPY-Y2 receptors has been shown to
reduce NPY levels and enhance stress vulnerability. Here, we hypothesized that ELS
(maternal separation) as well as adult stress (AS, as swim stress) changes the
expression of hippocampal NPY-Y2 receptor gene. We investigated (i) if ELS and AS affect NPY-Y2 gene expression in the hippocampus of male mice via
DNA methylation (ii) if ELS-induced epigenetic changes exert a programming
effect on NPY-Y2 gene expression in response to AS. Animals were assigned to the
following experimental groups: 1) controls, 2) ELS exposure, 3) AS exposure, 4)
ELS+AS exposure. We found that ELS and AS have a main effect on NPY-Y2
gene expression and mean DNA-methylation. Especially, increased NPY-Y2 gene
expression was found in the AS animals compared to other groups. Also, decreased
mean DNA-methylation was found in the AS animals compared to control and ELS animals
and increased mean DNA-methylation in ELS+AS animals compared to AS animals. In
addition, we determined a strong negative correlation between NPY-Y2 gene
expression and mean DNA-methylation. In conclusion, ELS seems to have a protective programming effect on
NPY-Y2 gene expression in response to AS via DNA methylation. Therefore, it might
be considered that ELS induces protective effects in males against consecutive stressors
at later life periods.