The neuroprotective effects and transdifferentiation of astrocytes into dopaminergic neurons of Ginkgolide K on Parkinson' disease mice

Abstract

Parkinson's disease (PD) is a chronic and progressive movement disorder caused by the selective loss of midbrain dopaminergic neurons of unknown etiology. Up to now, although there is a great development on treatments of PD, cures with neuroprotective or nerve regenerative effects are underway for PD patients. Here we reported neuroprotective effects of Ginkgolide K (GK) when mice were upon acute MPTP exposure, in which GK ameliorated the gait dysfunction and dopaminergic neuron loss. GK exhibits its ability in immunomodulation, including switching microglia to M2 phenotype and decreasing the microglia-mediated inflammation, inhibiting peripheral CD4⁺IFN-γ⁺ and CD4⁺IL-17⁺ T cells and α-synuclein specific autoantibodies. The expression of neurotrophic factors BDNF, GDNF and NT-3 was promoted with a treatment of GK in MPTP mice brains. Notably, GK enhanced the expression of nestin in GFAP⁺ astrocytes followed by the transdifferentiation of astrocyte-to-neuron independent on the Wnt signaling although GK induced the expression of Wnt signaling on astrocytes. Based on these results, our work implicates a therapeutic potential of GK for protecting TH⁺ neurons by multiple and intercellular pathways to modify nerve regeneration in MPTP mice. However, its exactly cellular and molecular mechanisms need to be further explored and confirmed.

Keywords: Astrocyte; GK; MPTP; Neuroregeneration; Wnt singling pathway.