Evidence for ancestral programming of resilience in a two-hit stress model
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Date
2017
Authors
Faraji, Jamshid
Soltanpour, Nabiollah
Ambeskovic, Mirela
Zucchi, Fabiola C. R.
Beaumier, Pierre
Kovalchuk, Igor
Metz, Gerlinde A. S.
Journal Title
Journal ISSN
Volume Title
Publisher
Frontiers Media
Abstract
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.
Description
Sherpa Romeo green journal; open access
Keywords
Multigenerational prenatal stress , Ancestral stress , Stress resiliency , Skilled reaching , Silent cerebral ischemia , Mini stroke , Two-hit theory
Citation
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