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EphA1 Activation Induces Neuropathological Changes in a Mouse Model of Parkinson’s Disease Through the CXCL12/CXCR4 Signaling Pathway

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Abstract

There is increasing evidence that EphA1 is involved in the function and development of the central nervous system, especially in neuroinflammation. It has been found to affect the disease progression of Alzheimer’s disease (AD) by regulating the neuroinflammatory process. Neuroinflammation has always been regarded as the mechanism of the development of Parkinson’s disease (PD) and possible therapeutic targets. Therefore, it is worth studying whether EphA1 has a potential therapeutic value for PD. The purpose of this study is to investigate the effect of EphA1 in mice and PD cell models and its mechanism.

In this study, we verified the difference in expression of EphA1 and the effect and mechanism of EphA1 on neuropathological changes through Parkinson’s patient samples, Parkinson’s mice model, and Parkinson’s model prepared from SH-SY5Y cells in vitro.

EphA1 was highly expressed in the substantia nigra (SN) region of Parkinson mice and the Parkinson cell model, while the expression of tyrosine hydroxylase (TH) in the SN region of Parkinson mice was significantly reduced. After silenced EphA1 in the SH-SY5Y cell PD model, the expression levels of α-synuclein, inflammatory factors, and microglia-activated chemokine decreased. The co-immunoprecipitation experiment proved that EphA1 overexpression could promote the binding of CXCL12 and CXCR4. However, after silenced EphA1 and CXCL12 at the same time, the above effects brought by silenced EphA1 were suppressed. The same result appeared in mice with PD.

EphA1 improves the inflammatory responses and neuropathological changes of the PD model in vivo and in vitro through the CXCL12/CXCR4 signaling pathway.

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Data Availability

All data generated or analyzed during this study are included in this published article.

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Funding

This work was supported by the Henan Province Science and Technology Development Plan (Grant No.: 192102310085) and Henan Province Medical Science and Technology Research Program (Grant No.: 201701018).

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Authors and Affiliations

  1. Department of Neurology, Henan Provincial People’s Hospital, No. 7 Weiwu Road, Zhengzhou, 450003, Henan, China

    Jianjun Ma, Zhidong Wang, Siyuan Chen, Wenhua Sun, Qi Gu, Dongsheng Li, Jinhua Zheng, Hongqi Yang & Xue Li

  2. People’s Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou, 450003, Henan, China

    Jianjun Ma, Zhidong Wang, Siyuan Chen, Wenhua Sun, Qi Gu, Dongsheng Li, Jinhua Zheng, Hongqi Yang & Xue Li

  3. People’s Hospital of Henan University, No. 7 Weiwu Road, Zhengzhou, 450003, Henan, China

    Jianjun Ma, Siyuan Chen, Qi Gu, Dongsheng Li, Jinhua Zheng, Hongqi Yang & Xue Li

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  1. Jianjun Ma
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Contributions

Conceptualization: Jianjun Ma; Methodology: Jianjun Ma, Zhidong Wang, and Siyuan Chen; Formal analysis and investigation: Jianjun Ma, Zhidong Wang, Wenhua Sun, Qi Gu, Dongsheng Li, Jinhua Zheng, Hongqi Yang, and Xue Li; Data visualization: Qi Gu, Dongsheng Li, and Jinhua Zheng; Literature search: Hongqi Yang and Xue Li; Writing of original draft preparation: Jianjun Ma and Zhidong Wang; Writing-review and editing: Jianjun Ma and Siyuan Chen; Funding acquisition: Jianjun Ma; Supervision: Jianjun Ma.

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Correspondence to Jianjun Ma.

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The experimental operation process is approved and supervised by the Ethics Committee of Henan Provincial People’s Hospital and Animal Protection and Use Agency Committee of Henan Provincial People’s Hospital.

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Highlights

1. EphA1 is highly expressed in Parkinson’s disease (PD) model and patients.

2. The effect of EphA1 and CXCL12 was studied on PD model in vitro and in vivo.

3. EphA1 overexpression promotes neuroinflammation and damage to dopaminergic neurons.

4. EphA1 activation induces neuropathological changes through the CXCL12/CXCR4 axis.

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Ma, J., Wang, Z., Chen, S. et al. EphA1 Activation Induces Neuropathological Changes in a Mouse Model of Parkinson’s Disease Through the CXCL12/CXCR4 Signaling Pathway. Mol Neurobiol 58, 913–925 (2021). https://doi.org/10.1007/s12035-020-02122-x

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