Fasudil is a clinically approved Rho-associated protein kinase (ROCK) inhibitor that has been used widely to treat cerebral consequences of subarachnoid hemorrhage. It is known to have a positive effect on animal models of neurological disorders including Parkinson's disease and stroke. However, its cellular effect on progenitor populations and differentiation is not clearly understood. While recent studies suggest that fasudil promotes the mobilization of neural stem cells (NSCs) from the subventricular zone in vivo and promotes the differentiation of the C17.2 cerebellar neuroprogenitor line in vitro, it is unclear whether fasudil is involved in the differentiation of primary NSCs. Here, we tested the effect of fasudil on mouse NSCs in vitro, and observed increased gliogenesis in NSCs derived from lateral ventricles. Upon treatment, fasudil promoted characteristics of neurogenesis including phenotypic changes in neural outgrowth and interkinetic nuclear-like movements as an immediate response, while Sox2 expression was maintained and GFAP expression increased. Moreover, the gliogenic response to fasudil medium was observed in both early postnatal and adult NSC cultures. Taken together, our results show that fasudil promotes the differentiation of NSCs into astroglial lineage, suggesting that it could be used to develop novel vitro gliogenesis models and regulate differentiation for neural repair.

Exposure to the ROCK inhibitor fasudil promotes gliogenesis of neural stem cells in vitro

Sottile V.
2018-01-01

Abstract

Fasudil is a clinically approved Rho-associated protein kinase (ROCK) inhibitor that has been used widely to treat cerebral consequences of subarachnoid hemorrhage. It is known to have a positive effect on animal models of neurological disorders including Parkinson's disease and stroke. However, its cellular effect on progenitor populations and differentiation is not clearly understood. While recent studies suggest that fasudil promotes the mobilization of neural stem cells (NSCs) from the subventricular zone in vivo and promotes the differentiation of the C17.2 cerebellar neuroprogenitor line in vitro, it is unclear whether fasudil is involved in the differentiation of primary NSCs. Here, we tested the effect of fasudil on mouse NSCs in vitro, and observed increased gliogenesis in NSCs derived from lateral ventricles. Upon treatment, fasudil promoted characteristics of neurogenesis including phenotypic changes in neural outgrowth and interkinetic nuclear-like movements as an immediate response, while Sox2 expression was maintained and GFAP expression increased. Moreover, the gliogenic response to fasudil medium was observed in both early postnatal and adult NSC cultures. Taken together, our results show that fasudil promotes the differentiation of NSCs into astroglial lineage, suggesting that it could be used to develop novel vitro gliogenesis models and regulate differentiation for neural repair.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/1326726
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