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Matrine Treatment Blocks NogoA-Induced Neural Inhibitory Signaling Pathway in Ongoing Experimental Autoimmune Encephalomyelitis

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A Correction to this article was published on 18 May 2022

An Erratum to this article was published on 20 January 2017

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Abstract

Myelin-associated inhibitors, such as NogoA, myelin-associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp), play a pivotal role in the lack of neuroregeneration in multiple sclerosis, an inflammatory demyelinating disease of the central nervous system (CNS). Matrine (MAT), a monomer that is used in traditional Chinese medicine as an anti-inflammatory agent, has shown beneficial effects in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, the underlying mechanisms of MAT-induced EAE amelioration are not fully understood. In the present study, we show that MAT treatment suppressed ongoing EAE, and this effect correlated with an increased expression of growth-associated protein 43, an established marker for axonal regeneration. MAT treatment significantly reduced the levels of NogoA, its receptor complex NgR/p75NTR/LINGO-1, and their downstream RhoA/ROCK signaling pathway in the CNS. In contrast, intracellular cyclic AMP (cAMP) levels and its protein kinase (protein kinase A (PKA)), which can promote axonal regrowth by inactivating the RhoA, were upregulated. Importantly, adding MAT in primary astrocytes in vitro largely induced cAMP/PKA expression, and blockade of cAMP significantly diminished MAT-induced expression of PKA and production of BDNF, a potent neurotrophic factor for neuroregeneration. Taken together, our findings demonstrate that the beneficial effects of MAT on EAE can be attributed not only to its capacity for immunomodulation, but also to its directly promoting regeneration of the injured CNS.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (no. 31570357), the Henan Province Science and Technology Development Plan (No. 152102310044), and the Henan Province Chinese Medicine Research Institute, China. The authors thank Katherine Regan for editorial assistance.

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Authors and Affiliations

  1. Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China

    Quan-Cheng Kan, Hui-Jun Zhang, Ming-Liang Zhang, Nan Liu, Yao-Juan Chu & Lin Zhu

  2. Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi’an, China

    Yuan Zhang & Xing Li

  3. Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China

    Yu-Ming Xu

  4. Department of Neurology, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Rodolfo Thome & Guang-Xian Zhang

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  1. Quan-Cheng Kan
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Correspondence to Guang-Xian Zhang or Lin Zhu.

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All efforts were made to reduce animal suffering, and the Institutional Committee on Care and Use of Research Animals approved the procedures used in this study.

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The authors declare that that they have no conflict of interest.

Additional information

The original version of this article was revised: The name of author Li Zhu was changed to Lin Zhu as requested by authors.

Quan-Cheng Kan and Hui-Jun Zhang have an equal contribution to this article.

An erratum to this article is available at https://doi.org/10.1007/s12035-017-0410-0.

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Kan, QC., Zhang, HJ., Zhang, Y. et al. Matrine Treatment Blocks NogoA-Induced Neural Inhibitory Signaling Pathway in Ongoing Experimental Autoimmune Encephalomyelitis. Mol Neurobiol 54, 8404–8418 (2017). https://doi.org/10.1007/s12035-016-0333-1

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