中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (10): 1743-1752.doi: 10.4103/1673-5374.238615

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

共聚物1促进脉络丛中白细胞介素-10和生长因子的释放而诱导神经发生

  

  • 收稿日期:2018-07-12 出版日期:2018-10-15 发布日期:2018-10-15

Release of interleukin-10 and neurotrophic factors in the choroid plexus: possible inductors of neurogenesis following copolymer-1 immunization after cerebral ischemia

Yolanda Cruz1, 2, 5, Edna E. García1, Jessica V. Gálvez1, Stella V. Arias-Santiago1, Horacio G. Carvajal1, Raúl Silva-García3, Herlinda Bonilla-Jaime2, Julio Rojas-Castañeda4, Antonio Ibarra1   

  1. 1 Centro de Investigación en Ciencias de la Salud (CICSA), FCS, Universidad Anáhuac México Norte, Huixquilucan, Estado de México, México
    2 Lab. De Biología de la reproducción, UAMI. Ciudad de México, México
    3 Hospital de Pediatría CMN Siglo XXI. Ciudad de México, México
    4 Subdirección de Medicina Experimental, Instituto Nacional de Pediatría.Ciudad de México, México
    5 Doctorado en Ciencias Biológicas, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Unidad Iztapalapa.Ciudad de México, México
  • Received:2018-07-12 Online:2018-10-15 Published:2018-10-15
  • Contact: Antonio Ibarra, PhD,jose.ibarra@anahuac.mx.
  • Supported by:

    This study was supported by a grant from Universidad Anahuac México Norte (No. 201425).

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摘要：

共聚物1是一种具有免疫调节性质的肽，经美国食品和药物管理局（FDA）批准用于治疗多发性硬化症。已有研究显示共聚物1在脑缺血模型中发挥神经保护作用并诱导神经发生。然而，该化合物的神经源性作用机制仍然未知。脉络丛（CP）是构成免疫与中枢神经系统之间界面的细胞网络，其可通过释放细胞因子和生长因子介导神经发生；因此，脉络丛可能在共聚物1诱导的神经发生中起作用。为了确定CP在共聚物1免疫后诱导脑缺血后神经发生中的作用，实验评估了脑缺血后14天脉络丛中生长因子（脑源性神经营养因子、胰岛素样生长因子1和神经营养因子3）和细胞因子（肿瘤坏死因子α、干扰素γ、白细胞介素4、白细胞介素10和白细胞介素17）的基因表达，同时分析了这些基因的表达与神经发生之间的相关性。结果表明，共聚物1能够刺激脉络丛中脑源性神经营养因子、胰岛素样生长因子1和神经营养因子3和白细胞介素10基因表达的上调，这与脑室下层和海马颗粒细胞层内神经发生的增加有关。实验证明了共聚物1对脉络丛中生长因子和白细胞介素10表达的影响，提出了共聚物1的神经源性作用机制。

orcid:0000-0003-2489-4689(Antonio Ibarra)

关键词: 脉络丛, 生长因子, 免疫调节, 保护性自身免疫, 共聚物1, 帕松, 脑卒中, 醋酸格拉替雷, tMCAo, 局灶性脑缺血

Abstract:

Copolymer-1 (Cop-1) is a peptide with immunomodulatory properties, approved by the Food and Drug Administration of United States in the treatment of multiple sclerosis. Cop-1 has been shown to exert neuroprotective effects and induce neurogenesis in cerebral ischemia models. Nevertheless, the mechanism involved in the neurogenic action of this compound remains unknown. The choroid plexus (CP) is a network of cells that constitute the interphase between the immune and central nervous systems, with the ability to mediate neurogenesis through the release of cytokines and growth factors. Therefore, the CP could play a role in Cop-1-induced neurogenesis. In order to determine the participation of the CP in the induction of neurogenesis after Cop-1 immunization, we evaluated the gene expression of various growth factors (brain-derived neurotrophic factor, insulin-like growth factor 1, neurotrophin-3) and cytokines (tumor necrosis factor alpha, interferon-gamma, interleukin-4 (IL-4), IL-10 and IL-17), in the CP at 14 days after ischemia. Furthermore, we analyzed the correlation between the expression of these genes and neurogenesis. Our results showed that Cop-1 was capable of stimulating an upregulation in the expression of the genes encoding for brain-derived neurotrophic factor, insulin-like growth factor 1, neurotrophin-3 and IL-10 in the CP, which correlated with an increase in neurogenesis in the subventricular and subgranular zone. As well, we observed a downregulation of IL-17 gene expression. This study demonstrates the effect of Cop-1 on the expression of growth factors and IL-10 in the CP, in the same way, presents a possible mechanism involved in the neurogenic effect of Cop-1.

Key words: choroid plexus, growth factors, immunomodulation, protective autoimmunity, Cop-1, Copaxone, stroke, glatiramer acetate, tMCAo, focal cerebral ischemia