神经连接蛋白1、2对少突胶质细胞分化与髓鞘形成的促进作用

张小娇; 汤欣

doi:10.16098/j.issn.0529-1356.2024.02.001

PDF(3670 KB)

解剖学报 ›› 2024, Vol. 55 ›› Issue (2) : 125-132. DOI: 10.16098/j.issn.0529-1356.2024.02.001

神经生物学

神经连接蛋白1、2对少突胶质细胞分化与髓鞘形成的促进作用

张小娇朱明媚王家彦汤欣*

作者信息 +

Positive effects of neuroligin-1, -2 on oligodendrocyte differentiation and myelination

ZHANG Xiao-jiao ZHU Ming-mei WANG Jia-yan TANG Xin*

Author information +

文章历史 +

摘要

目的探讨神经连接蛋白1、2（NLGN-1、-2）对少突胶质细胞（OLs）分化和中枢神经系统髓鞘形成的作用。方法体外培养OLs，用不同浓度(80 μg/L、200 μg/L、500 μg/L)的NLGN-1、-2处理细胞，通过免疫荧光染色观察OLs的分化，利用Real-time PCR检测髓鞘相关基因的表达，利用Western blotting技术检测髓鞘相关蛋白的表达。结果 NLGN-1、-2能够促进少突胶质前体细胞(OPCs)分化为成熟的OLs，提高OLs髓鞘形成的能力,且在体外条件下500 μg/L促进效果最优，NLGN-2的促进效果优于NLGN-1。同时，Real-time PCR检测到最佳浓度处理后髓鞘相关基因髓磷脂P0蛋白（MPZ）、髓磷脂碱性蛋白（MBP）的mRNA表达水平升高。Western blotting 结果表明，500 μg/L NLGN-1和NLGN-2处理OLs 12 h后MBP和MPZ蛋白表达量显著升高。结论 NLGN-1、-2能够促进OLs分化进而提高OLs髓鞘形成的能力,且NLGN-2的促进效果优于NLGN-1,提示加入抑制性突触的细胞因子有利于提高中枢胶质细胞的髓鞘形成能力。

Abstract

Objective To investigate the effects of neuroligin-1, -2 (NLGN-1,-2) on oligodendrocyte(OLs) differentiation and myelination in the central nervous system. Methods OLs were cultured in vitro in the presence of different concentrations of NLGN-1 and NLGN-2. Morphological differentiation of OLs was observed by immunofluorescent staining and mRNA expression levels of myelin-associated genes were detected by Real-time PCR. Western blotting was used to detect the expression of myelin-related proteins. Results NLGN-1, -2 accelerated the differentiation of oligodendrocyte precursor cells (OPCs) into mature OLs, and promoted the ability of myelin sheath formation. In vitro culture conditions, the dosage of 500 μg/L had the best promotion effect on OLs differentiation and maturation, and NLGN-2 had better promoting effect than that of NLGN-1. Furthermore, the mRNA expression levels of myelin-associated genes myelin protein P0(MPZ), myelin basic protein(MBP) increased after the neuroligins treatments detected by Real-time PCR. Western blotting result showed that the expressions of MBP and MPZ increased significantly after 500 μg/L treatment with NLGN-1 and NLGN-2 for 12 hours. Conclusion NLGN-1, -2 promote OLs differentiation and myelination. The positive effect of NLGN-2 is greater than that of NLGN-1 significantly, suggesting that the treatment with inhibitory synaptic-associated cytokines may improve the ability of myelin sheath formation in the central nervous system.

导出引用

张小娇朱明媚王家彦汤欣. 神经连接蛋白1、2对少突胶质细胞分化与髓鞘形成的促进作用[J]. 解剖学报. 2024, 55(2): 125-132 https://doi.org/10.16098/j.issn.0529-1356.2024.02.001

ZHANG Xiao-jiao ZHU Ming-mei WANG Jia-yan TANG Xin. Positive effects of neuroligin-1, -2 on oligodendrocyte differentiation and myelination[J]. Acta Anatomica Sinica. 2024, 55(2): 125-132 https://doi.org/10.16098/j.issn.0529-1356.2024.02.001

中图分类号： Q421

参考文献

［1］Ramírez-Jarquín UN, Lazo-Gómez R, Tovar YRLB, et al. Spinal inhibitory circuits and their role in motor neuron degeneration［J］. Neuropharmacology, 2014, 82(2014): 101-107.

［2］Pohl TT, Hörnberg H. Neuroligins in neurodevelopmental conditions: how mouse models of de novo mutations can help us link synaptic function to social behavior［J］. Neuronal Signal, 2022, 6(2): Ns20210030.

［3］Ouyang JL, Zhu XH. Research and application prospect based on Neuroligins ［J］. Journal of Hebei Medical University, 201,42(2):246-249.(in Chinese)

欧阳俊琳,朱小虎.基于神经连接蛋白Neuroligins的研究及应用前景［J］.河北医科大学学报,2021,42(2):246-249.

［4］Nguyen QA, Horn ME, Nicoll RA. Distinct roles for extracellular and intracellular domains in neuroligin function at inhibitory synapses［J］. Elife, 2016, 5(2016): e19236.

［5］Ali H, Marth L, Krueger-Burg D. Neuroligin-2 as a central organizer of inhibitory synapses in health and disease［J］. Sci Signal, 2020, 13(663):eabd8379.

［6］Liu X, Hua F, Yang D, et al. Roles of neuroligins in central nervous system development: focus on glial neuroligins and neuron neuroligins［J］. J Transl Med, 2022, 20(1): 418.

［7］Barnabé-Heider F, Göritz C, Sabelström H, et al. Origin of new glial cells in intact and injured adult spinal cord［J］. Cell Stem Cell, 2010, 7(4): 470-482.

［8］Moura DMS, Brennan EJ, Brock R, et al. Neuron to oligodendrocyte precursor cell synapses: protagonists in oligodendrocyte development and myelination, and targets for therapeutics［J］. Front Neurosci, 2021, 15(2022): 779125.

［9］Ghelman J, Grewing L, Windener F, et al. SKAP2 as a new regulator of Oligodendroglial migration and myelin sheath formation［J］. Glia, 2021, 69(11): 2699-2716.

［10］Fünfschilling U, Supplie LM, Mahad D, et al. GlycOLytic oligodendrocytes maintain myelin and long-term axonal integrity［J］. Nature, 2012, 485(7399): 517-521.

［11］Fan B, Wei Z, Feng S. Progression in translational research on spinal cord injury based on microenvironment imbalance［J］. Bone Res, 2022, 10(1): 35.

［12］Kipp M. Oligodendrocyte physiology and pathology function［J］. Cells, 2020, 9(9):2078.

［13］Duncan GJ, Manesh SB, Hilton BJ, et al. The fate and function of oligodendrocyte progenitor cells after traumatic spinal cord injury［J］. Glia, 2020, 68(2): 227-245.

［14］Ramírez-Jarquín UN, Tapia R. Excitatory and inhibitory neuronal circuits in the spinal cord and their role in the control of motor neuron function and degeneration［J］. ACS Chem Neurosci, 2018, 9(2): 211-216.

［15］Qin L, Guo S, Han Y, et al. Functional mosaic organization of neuroligins in neuronal circuits［J］. Cell MOL Life Sci, 2020, 77(16): 3117-3127.

［16］Luo JK, Melland H, Nithianantharajah J, et al. Postsynaptic neuroligin-1 mediates presynaptic endocytosis during neuronal activity［J］. Front Mol Neurosci, 2021, 14(2021): 744845.

［17］Zhang G, Sun Y, Wu ZS, et al. Clinical relevance and prognostic value of the neuronal protein neuroligin 2 in breast cancer［J］. Front Oncol, 2021, 11(2020): 630257.

［18］Chen J, Dong B, Feng X, et al. Aberrant mPFC GABAergic synaptic transmission and fear behavior in neuroligin-2 R215H knock-in mice［J］. Brain Res, 2020, 1730(2020): 146671.

［19］Stogsdill JA, Ramirez J, Liu D, et al. Astrocytic neuroligins control astrocyte morphogenesis and synaptogenesis［J］. Nature, 2017, 551(7679): 192-197.

［20］Farhy-Tselnicker I, Allen NJ. Astrocytes, neurons, synapses: a tripartite view on cortical circuit development［J］. Neural Dev, 2018, 13(1): 7.

［21］Karram K, Chatterjee N, Trotter J. NG2-expressing cells in the nervous system: role of the proteoglycan in migration and glial-neuron interaction［J］. J Anat, 2005, 207(6): 735-744.

［22］Proctor DT, Stotz SC, Scott L OM, et al. Axo-glial communication through neurexin-neuroligin signaling regulates myelination and Oligodendrocyte differentiation［J］. Glia, 2015, 63(11): 2023-2039.

［23］Kathuria A, Lopez-Lengowski K, Watmuff B, et al. Synaptic deficits in iPSC-derived cortical interneurons in schizophrenia are mediated by NLGN2 and rescued by N-acetylcysteine［J］. Transl Psychiatry, 2019, 9(1): 321.

［24］Meng YX, Chu L, Xu Zh, et al. Induced experimental autoimmune encephalomyelitis shows the different phenotype of disease in C57BL/6 mice with myelin Oligodendrocyte glycoprotein 35-55［J］. Acta Anatomica Sinica, 2020, 51(4): 483-490.（in Chinese）

蒙延筱, 楚兰, 徐竹, 等. 髓鞘少突胶质细胞糖蛋白35~55肽段诱导C57BL/6 小鼠实验性自身免疫性脑脊髓炎疾病表型［J］, 2020, 51(4): 483-490.

［25］Miyata S. Cytoskeletal signal-regulated oligodendrocyte myelination and remyelination［J］. Adv Exp Med Biol, 2019, 1190(2019): 33-42.

［26］Yamamoto K, Yamamoto T, Honjo K, et al. Electrical stimulation with periodic alternating intervals stimulates neuronal cells to produce neurotrophins and cytokines through activation of mitogen-activated protein kinase pathways［J］. Eur J Oral Sci, 2015, 123(6): 403-408.

［27］Falcicchia C, Tozzi F, Arancio O, et al. Involvement of p38 MAPK in synaptic function and dysfunction［J］. Int J MOL Sci, 2020, 21(16):5624.

［28］Santra M, Chopp M, Zhang ZG, et al. Thymosin β 4 mediates oligodendrocyte differentiation by upregulating p38 MAPK［J］. Glia, 2012, 60(12): 1826-1838.