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Citation |
Faraji J, Soltanpour N, Ambeskovic M, Zucchi FCR, Beaumier P, Kovalchuk I, Metz GAS. Front. Behav. Neurosci. 2017; 11: e89. |
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Affiliation |
Canadian Centre for Behavioural Neuroscience (CCBN), University of LethbridgeLethbridge, AB, Canada. |
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Copyright |
(Copyright © 2017, Frontiers Research Foundation) |
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DOI |
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PMID |
28553212 |
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PMCID |
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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. Language: en |
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Keywords |
ancestral stress; mini stroke; multigenerational prenatal stress; silent cerebral ischemia; skilled reaching; stress resiliency; two-hit theory |