Ginsenoside Rg1 promotes astrocyte-to-neuron transdifferentiation in rat and its possible mechanism.

Abstract

Neuronal loss caused by spinal cord injury (SCI) usually contributes to irreversible motor dysfunction. Promoting neuronal regeneration and functional recovery is vital to the repair of SCI. Astrocytes, activated by SCI with high proliferative capacity and proximity to neuronal lineage, are considered ideal cells for neuronal regeneration. As previous studies identified several small molecules for the induction of astrocyte-to-neuron, we confirmed that ginsenoside Rg1, a neuroprotective herb, could promote the direct transdifferentiation of astrocyte-to-neuron in rat. Immunofluorescence staining showed that 26.0 ± 1.5% of the induced cells exhibited less astroglial properties and more neuronal markers with typical neuronal morphologies, reflecting 20.6 ± 0.9% of cholinergic neurons and 22.3 ± 1.9% of dopaminergic neurons. Western blot and qRT-PCR revealed that the induced cells had better antiapoptotic ability and Rg1-promoted neuronal transdifferentiation of reactive astrocytes might take effect through suppressing Notch/Stat3 signal pathway. In vivo, a revised SCI model treated by Rg1 was confirmed with faster functional recovery and less injury lesion cavity. In summary, our study provided a novel strategy of direct transdifferentiation of endogenous rat reactive astrocytes into neurons with Rg1 and promotion of neuronal regeneration after SCI.