SKP-SCs transplantation alleviates 6-OHDA-induced dopaminergic neuronal injury by modulating autophagy

Chengxiao Ma,Maohong Cao,Kefu Cai,Wen Zhang,Wengcong Wang,Mei Liu,Jiabing Shen

doi:10.1038/s41419-021-03967-3

Chengxiao Ma, Maohong Cao + Show 5 more

Open Access

https://doi.org/10.1038/s41419-021-03967-3

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Abstract

Parkinson’s disease is a common neurodegenerative disease. Cell transplantation is a promising therapeutic option for improving the survival and function of dopaminergic neurons, but the mechanisms underlying the interaction between the transplanted cells and the recipient neurons remain to be studied. In this study, we investigated the effects of skin precursor cell-derived Schwann cells (SKP-SCs) directly cocultured with 6-OHDA-injured dopaminergic neurons in vitro and of SKP-SCs transplanted into the brains of 6-OHDA-induced PD mice in vivo. In vitro and in vivo studies revealed that SKP-SCs could reduce the damage to dopaminergic neurons by enhancing self-autophagy and modulating neuronal autophagy. Thus, the present study provides the first evidence that cell transplantation mitigates 6-OHDA-induced damage to dopaminergic neurons by enhancing self-autophagy, suggesting that earlier transplantation of Schwann cells might help alleviate the loss of dopaminergic neurons.

Highlights

Parkinson’s disease (PD) is a neurodegenerative disease that is principally defined by the motor symptoms of resting tremor, rigidity, and bradykinesia
Activation of autophagy has been observed in 6-OHDA-induced PD models, and modulation of oxidative stress-induced excessive autophagy on dopaminergic neuronal damage is a promising strategy for the treatment of PD [46]
Further studies revealed that skin precursor cell-derived Schwann cells (SKP-SCs) affected the autophagy of cocultured neurons or retinoic acid (RA)-SY5Y cells in vitro by enhancing self-autophagy, avoiding excessive autophagy induced by oxidative stress, and enhancing cell survival

Summary

INTRODUCTION

Parkinson’s disease (PD) is a neurodegenerative disease that is principally defined by the motor symptoms of resting tremor, rigidity, and bradykinesia. We verified our hypothesis using primary mouse mesencephalic neurons, retinoic acid-differentiated expected, the neurons in the monoculture group showed a rapid increase in LC3b fluorescence after injury and a decrease in fluorescence while maintaining a high level of autophagy for SH-SY5Y (RA-SY5Y) cells and mice, and we proposed the some time (Fig. 2D-Mo, Supplementary Fig. 3A). This decrease was mechanism through which SKP-SCs protect dopaminergic neurons.

RESULTS

Ma et al 3

DISCUSSION

Findings

MATERIALS AND METHODS