Neuroprotective effect of olfactory ensheathing cells co-transfected with Nurr1 and Ngn2 in both in vitro and in vivo models of Parkinson's disease

作者：Liu, Qingqing; Qin, Qi; Sun, Hongxue; Zhong, Di; An, Ran; Tian, Yushuang; Chen, Hongping; Jin, Jing; Wang, Haining; Li, Guozhong^*

来源：Life Sciences, 2018, 194: 168-176.

DOI：10.1016/j.lfs.2017.12.038

• Parkinson's disease
• Olfactory ensheathing cells
• Nuclear receptor-related factor 1
• Neurogenin 2
• Cell transplantation therapy

Aims: The aim of the study is to evaluate the neuroprotective effects of olfactory ensheathing cells (OECs) with the overexpression of nuclear receptor-related factor 1 (Nurr1) and neurogenin 2 (Ngn2) in experimental models of Parkinson's disease (PD) and to elucidate the potential mechanism underlying the neuroprotective effects of OECs-Nurr1-Ngn2. @@@ Materials and methods: In vitro study, OECs-Nurr1-Ngn2 conditioned medium (CM) was added to MPP+ -treated PC12 cells for 24 h, and then the viability of PC12 cells, oxidative stress and apoptosis were detected. In vivo study, 48 male Sprague-Dawley (SD) rats were randomly divided into four groups. OECs/VMCs and OECs-Nurr1-Ngn2/VMCs groups were transplanted with 2 x 10(5) cells each of OECs or OECs-Nurr1-Ngn2 and VMCs into the right striatum one week after a unilateral 6-OHDA lesion. Control and PD groups were injected with 0.9% NaCl and 0.2% ascorbic acid into the same region. Rotational behavior was determined at 2, 4, 6 and 8 weeks after injection or implantation in all groups. Neuronal differentiation markers, oxidative stress-and apoptosis-related indicators were detected at 8 weeks post-grafting. @@@ Key findings: OECs-Nurr1-Ngn2 increased the viability of PC12 cells, inhibited oxidative stress and apoptosis, and these effects could be reversed by pre-treatment of k252a, a TrkB receptor inhibitor. The behavioral deficits of PD rat were ameliorated by the transplantation of OECs-Nurr1-Ngn2/VMCs.

• 出版日期2018-2-1
• 单位哈尔滨医科大学