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 in MPS rats along with upregulation of its predicted target genes Mapk10 and Rasd2. The findings indicate that MPS generates adaptive flexibility in movement, which is challenged by a second stressor, such as a neuropathological condition.
Prenatal stress PS is one of the most critical determinants of health and disease Cottrell and Seckl, PS is associated with poor health later in life, including a higher risk of hypertension and cardio- and cerebrovascular disease Igosheva et al. Moreover, stress has been recognized as a critical variable in stroke risk and recovery Kirkland et al. Indeed, stress represents a critical regulator of metabolic and cardiovascular function and is the cause of hypertension, the number one risk factor for stroke Kulkarni et al.
Experimental evidence revealed that PS is associated with poor stroke outcome Wang et al. Accordingly, PS impedes recovery after ischemic lesion with associated transcriptomic changes Zucchi et al. PS has long-term consequences on fetal endocrine function involving the hypothalamic-pituitary-adrenal HPA axis Harris and Seckl, Prenatal programming of HPA axis properties may explain the large variability in recovery among stroke patients Nudo, In prenatally stressed individuals, the experience of a stroke may represent a second hit to the dysregulated HPA axis and challenge neural plasticity with inflammation, hypoxia-ischemia, neuronal death and neurodegenerative processes Craft and Devries, In addition, patients with stroke frequently report that they experience difficulties in coping with stress Green and King, or experience emotional and psychological distress Duric et al.
The consequences of PS are potentially carried forward through several generations of offspring Dias and Ressler, ; Gapp et al. Through epigenetic mechanisms, such as microRNA miRNA expression, PS can alter stress response, motor function and health trajectories of subsequent generations, with pronounced changes when challenged with recurrent stress Ward et al.
