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

dc.contributor.authorFaraji, Jamshid
dc.contributor.authorSoltanpour, Nabiollah
dc.contributor.authorAmbeskovic, Mirela
dc.contributor.authorZucchi, Fabiola C. R.
dc.contributor.authorBeaumier, Pierre
dc.contributor.authorKovalchuk, Igor
dc.contributor.authorMetz, Gerlinde A. S.
dc.descriptionSherpa Romeo green journal; open accessen_US
dc.description.abstractIn 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.en_US
dc.identifier.citationFaraji, 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.2017.00089en_US
dc.publisherFrontiers Mediaen_US
dc.publisher.departmentDepartment of Biological Sciencesen_US
dc.publisher.departmentDepartment of Neuroscienceen_US
dc.publisher.facultyArts and Scienceen_US
dc.publisher.institutionUniversity of Lethbridgeen_US
dc.publisher.institutionGolestan University of Medical Sciences (GUMS)en_US
dc.publisher.institutionBabol University of Medical Sciencesen_US
dc.publisher.institutionUniversity of Brasiliaen_US
dc.publisher.institutionCanAlt Health Laboratoriesen_US
dc.subjectMultigenerational prenatal stressen_US
dc.subjectAncestral stressen_US
dc.subjectStress resiliencyen_US
dc.subjectSkilled reachingen_US
dc.subjectSilent cerebral ischemiaen_US
dc.subjectMini strokeen_US
dc.subjectTwo-hit theoryen_US
dc.subject.lcshStress tolerance (Psychology)
dc.subject.lcshTransient ischemic attack
dc.titleEvidence for ancestral programming of resilience in a two-hit stress modelen_US
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