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

作　　者：Yolanda Cruz Edna E.García Jessica V.Gálvez Stella V.Arias-Santiago Horacio G.Carvajal Raúl Silva-García Herlinda Bonilla-Jaime Julio Rojas-Castaneda Antonio Ibarra 

机构地区：[1]Centro de Investigación en Ciencias de la Salud (CICSA),FCS,Universidad Anáhuac México Norte Huixquilucan, Estado de México, México [2]Lab. De Biologia 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

出　　处：《Neural Regeneration Research》2018年第10期1743-1752,共10页中国神经再生研究（英文版）

基　　金：supported by a grant from Universidad Anahuac México Norte(No.201425)

摘　　要：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.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.

关 键 词：choroid plexus growth factors IMMUNOMODULATION protective autoimmunity Cop-1 COPAXONE stroke glatiramer acetate t MCAo focal cerebral ischemia 

分 类 号：R743[医药卫生—神经病学与精神病学]