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神经干细胞移植联合硬脂酸乙酯通过促进神经干细胞迁移和分化改善 PD 大鼠的运动行为。

Neural stem cells transplantation combined with ethyl stearate improve PD rats motor behavior by promoting NSCs migration and differentiation.

机构信息

School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

Research Center of Integrative Medicine (Key Laboratory of Chinese Medicine Pathogenesis and Therapy Research), School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

出版信息

CNS Neurosci Ther. 2023 Jun;29(6):1571-1584. doi: 10.1111/cns.14119. Epub 2023 Mar 16.

Abstract

BACKGROUND

In recent years, the ability of neural stem cells (NSCs) transplantation to treat Parkinson's disease (PD) has attracted attention. However, it is still a challenge to promote the migration of NSCs to the lesion site and their directional differentiation into dopaminergic neurons in PD. C-C motif chemokine ligand 5 (CCL5) and C-C motif chemokine receptor 5 (CCR5) are expressed in the brain and are important regulators of cell migration. It has been reported that ethyl stearate (PubChem CID: 8122) has a protective effect in 6-OHDA-induced PD rats.

METHODS

Parkinson's disease rats were injected with 6-hydroxydopamine (6-OHDA) into the right substantia nigra, and striatum followed by 8 μL of an NSC cell suspension containing 100 μM ethyl stearate and 8 × 10 cells in the right striatum. The effect of transplantation NSCs combined with ethyl stearate was assessed by evaluating apomorphine (APO)-induced turning behavior and performance in the pole test. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting (WB), and immunofluorescence staining were also performed.

RESULTS

NSCs transplantation combined with ethyl stearate ameliorated the behavioral deficits of PD rats. PD rats that received transplantation NSCs combined with ethyl stearate exhibited increased expression of tyrosine hydroxylase (TH) and an increased number of green fluorescent protein (GFP)-positive cells. Furthermore, GFP-positive cells migrated into the substantia nigra and differentiated into dopaminergic neurons. The expression of CCL5 and CCR5 was significantly increased after transplantation NSCs combined with ethyl stearate.

CONCLUSIONS

These findings suggest that NSCs transplantation combined with ethyl stearate can improve the motor behavioral performance of PD rats by promoting NSCs migration from the striatum to the substantia nigra via CCL5/CCR5 and promoting the differentiation of NSCs into dopaminergic neurons.

摘要

背景

近年来,神经干细胞(NSCs)移植治疗帕金森病(PD)的能力引起了关注。然而,促进 NSCs 迁移到病变部位并使其定向分化为 PD 中的多巴胺能神经元仍然是一个挑战。CC 基序趋化因子配体 5(CCL5)和 CC 基序趋化因子受体 5(CCR5)在大脑中表达,是细胞迁移的重要调节剂。据报道,硬脂酸乙酯(PubChem CID:8122)在 6-羟基多巴胺(6-OHDA)诱导的 PD 大鼠中具有保护作用。

方法

将 6-OHDA 注入右侧黑质和纹状体,随后将含有 100μM 硬脂酸乙酯和 8×10 的 NSC 细胞悬液 8μL 注入右侧纹状体,对 NSCs 移植联合硬脂酸乙酯的效果进行评估。通过评估阿扑吗啡(APO)诱导的旋转行为和杆试验中的表现来评估。还进行了定量实时逆转录聚合酶链反应(qRT-PCR)、Western blot(WB)和免疫荧光染色。

结果

NSCs 移植联合硬脂酸乙酯改善了 PD 大鼠的行为缺陷。接受 NSCs 移植联合硬脂酸乙酯治疗的 PD 大鼠酪氨酸羟化酶(TH)表达增加,绿色荧光蛋白(GFP)阳性细胞数量增加。此外,GFP 阳性细胞迁移到黑质并分化为多巴胺能神经元。移植 NSCs 联合硬脂酸乙酯后,CCL5 和 CCR5 的表达明显增加。

结论

这些发现表明,NSCs 移植联合硬脂酸乙酯通过促进 CCL5/CCR5 从纹状体向黑质迁移,促进 NSCs 向多巴胺能神经元分化,可改善 PD 大鼠的运动行为表现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ed7/10173712/9230fe3fde7a/CNS-29-1571-g009.jpg

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