Epigenetic programming of the stress response in male and female rats by prenatal restraint stress

Muriel Darnaudéry, Stefania Maccari
Brain Research Reviews. 2008-03-01; 57(2): 571-585
DOI: 10.1016/j.brainresrev.2007.11.004

PubMed
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Exposure to hostile conditions results in a series of coordinated responses aimed
at enhancing the probability of survival. The activation of the
hypothalamo-pituitary-adrenocortical (HPA) axis plays a pivotal role in the
stress response. While the short-term activation of the HPA axis allows adaptive
responses to the challenge, in the long run this can be devastating for the
organism. In particular, life events occurring during the perinatal period have
strong long-term effects on the behavioral and neuroendocrine response to
stressors. In male and female rats exposed to prenatal restraint stress (PRS),
these effects include a long-lasting hyperactivation of the HPA response
associated with an altered circadian rhythm of corticosterone secretion.
Furthermore, male animals exhibit sleep disturbances. In males, these HPA
dysfunctions have been reported in infant, young, adult and aged animals, thus
suggesting a permanent effect of early stress. Interestingly, after exposure to
an intense inescapable footshock, female PRS rats durably exhibit a blunted
corticosterone secretion response to stress. In male PRS rats exposed to an
alcohol challenge, the HPA axis is similarly hyporesponsive. Rats exposed to PRS
also show behavioral disturbances. Both male and female PRS rats show high
anxiety levels and depression-like behavior during adulthood, although some
studies suggest that female PRS rats present low anxiety levels. With ageing,
male and female PRS rats exhibit memory impairments in hippocampus-dependent
tasks, while female PRS rats improve their memory performance during adulthood.
The gender effect on behavior seems to be related to a reduction in hippocampal
plasticity in male PRS rats, and an increase in female PRS rats. Despite the
permanent imprinting induced by early stress, the dysfunctions observed after PRS
can be reversed by environmental or pharmacological strategies such as
environmental enrichment or antidepressive and neurotrophic treatments.
Mechanisms underlying the effects of PRS on the offspring remain largely unknown.
However, previous studies have demonstrated that maternal glucocorticoids during
pregnancy play an important role in the HPA disturbances reported in male
offspring. Finally, gestational stress has long-lasting effects on the HPA axis
and on behavior in the dams. Alterations in maternal behavior could thus also
make a strong contribution to the long-term effects of PRS, through epigenetic
mechanisms.

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