Evidence for ancestral programming of resilience in a two-hit stress model

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Faraji, Jamshid
Soltanpour, Nabiollah
Ambeskovic, Mirela
Zucchi, Fabiola C. R.
Beaumier, Pierre
Kovalchuk, Igor
Metz, Gerlinde A. S.
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Frontiers Media
In a continuously stressful environment, the effects of recurrent prenatal stress (PS) may accumulate across generations and alter stress vulnerability and resilience. Here, we report in female rats that a family history of recurrent ancestral PS facilitates certain aspects of movement performance, and that these benefits are abolished by the experience of a second hit, induced by a silent ischemia during adulthood. Female F4-generation rats with and without a family history of cumulative multigenerational PS (MPS) were tested for skilled motor function before and after the induction of a minor ischemic insult by endothelin-1 infusion into the primary motor cortex. MPS resulted in improved skilled motor abilities and blunted hypothalamic-pituitary-adrenal (HPA) axis function compared to non-stressed rats. Deep sequencing revealed downregulation of miR-708 in MPS rats along with upregulation of its predicted target genes Mapk10 and Rasd2. Through miR-708 stress may regulate mitogen-activated protein kinase (MAPK) pathway activity. Hair trace elemental analysis revealed an increased Na/K ratio, which suggests a chronic shift in adrenal gland function. The ischemic lesion activated the HPA axis in MPS rats only; the lesion, however, abolished the advantage of MPS in skilled reaching. The findings indicate that MPS generates adaptive flexibility in movement, which is challenged by a second stressor, such as a neuropathological condition. Thus, a second “hit” by a stressor may limit behavioral flexibility and neural plasticity associated with ancestral stress.
Sherpa Romeo green journal; open access
Multigenerational prenatal stress , Ancestral stress , Stress resiliency , Skilled reaching , Silent cerebral ischemia , Mini stroke , Two-hit theory
Faraji, J., Soltanpour, N., Ambeskovic, M., Zucchi, F. C. R., Beaumier, P., Kovalchuk, I., & Metz, G. A. S. (2017). Evidence for ancestral programming of resilience in a two-hit stress model. Frontiers in Behavioural Neuroscience, 11(89). doi10.3389/fnbeh.2017.00089