| First Author | Nguyen T | Year | 2018 |
| Journal | Proc Natl Acad Sci U S A | Volume | 115 |
| Issue | 41 | Pages | E9668-E9677 |
| PubMed ID | 30237284 | Mgi Jnum | J:266327 |
| Mgi Id | MGI:6202792 | Doi | 10.1073/pnas.1803384115 |
| Citation | Nguyen T, et al. (2018) Let-7i inhibition enhances progesterone-induced functional recovery in a mouse model of ischemia. Proc Natl Acad Sci U S A 115(41):E9668-E9677 |
| abstractText | Progesterone (P4) is a potent neuroprotectant and a promising therapeutic for stroke treatment. However, the underlying mechanism(s) remain unclear. Our laboratory recently reported that brain-derived neurotrophic factor (BDNF) is a critical mediator of P4's protective actions and that P4-induced BDNF release from cortical astrocytes is mediated by a membrane-associated progesterone receptor, Pgrmc1. Here, we report that the microRNA (miRNA) let-7i is a negative regulator of Pgrmc1 and BDNF in glia and that let-7i disrupts P4-induced BDNF release and P4's beneficial effects on cell viability and markers of synaptogenesis. Using an in vivo model of ischemia, we demonstrate that inhibiting let-7i enhances P4-induced neuroprotection and facilitates functional recovery following stroke. The discovery of such factors that regulate the cytoprotective effects of P4 may lead to the development of biomarkers to differentiate/predict those likely to respond favorably to P4 versus those that do not. |
