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Altered levels of immune cell adhesion molecules are associated with memory impairment in schizophrenia and healthy controls
Brain, Behavior, and Immunity ( IF 8.8 ) Pub Date : 2020-10-01 , DOI: 10.1016/j.bbi.2020.06.017
Helen Q Cai 1 , Thomas W Weickert 2 , Vibeke S Catts 1 , Ryan Balzan 3 , Cherrie Galletly 4 , Dennis Liu 5 , Maryanne O'Donnell 6 , Cynthia Shannon Weickert 2
Affiliation  

Increased cytokines and increased intercellular adhesion molecule-1 (ICAM1) found in the schizophrenia prefrontal cortex and in the blood may relate to cognitive deficits. Endothelial ICAM1 regulates immune cell trafficking into the brain by binding to integrins located on the surface of leukocytes. Whether the circulating levels of the main ICAM1 adhesion partners, lymphocyte-function associated antigen-1 (LFA1) and complement receptor 3 (CR3), both integrins, are altered in schizophrenia is unknown. Gene expressions of ICAM1, LFA1 and CR3 were measured in leukocytes from 86 schizophrenia patients and 77 controls. Participants were also administered cognitive testing to determine the extent to which cognitive ability was related to molecular measures of leukocyte adhesion. This cohort was previously stratified into inflammatory subgroups based on circulating cytokine mRNAs; thus, gene expressions were analysed by diagnosis and by inflammatory subgroups. Previously measured plasma ICAM1 protein was elevated in "high inflammation" schizophrenia compared to both "high" and "low inflammation" controls while ICAM1 mRNA was unchanged in leukocytes. LFA1 mRNA was decreased and CR3 mRNA was increased in leukocytes from people with schizophrenia compared to controls. LFA1 mRNA levels were positively correlated with working memory and elevated soluble ICAM1 was negatively correlated with verbal memory in schizophrenia. Altogether, some of the cognitive deficits in schizophrenia may be associated with altered expression of molecules that regulate immune cell trafficking.

中文翻译:

免疫细胞粘附分子水平的改变与精神分裂症和健康对照组的记忆障碍有关

在精神分裂症前额叶皮层和血液中发现的细胞因子增加和细胞间粘附分子 1 (ICAM1) 增加可能与认知缺陷有关。内皮 ICAM1 通过与位于白细胞表面的整合素结合来调节免疫细胞向大脑的运输。主要 ICAM1 粘附伙伴、淋巴细胞功能相关抗原 1 (LFA1) 和补体受体 3 (CR3) 的循环水平,这两种整合素在精神分裂症中是否发生改变尚不清楚。在来自 86 名精神分裂症患者和 77 名对照者的白细胞中测量了 ICAM1、LFA1 和 CR3 的基因表达。参与者还进行了认知测试,以确定认知能力与白细胞粘附分子测量的相关程度。该队列先前根据循环细胞因子 mRNA 分为炎症亚组。因此,通过诊断和炎症亚组分析基因表达。与“高”和“低炎症”对照相比,先前测量的血浆 ICAM1 蛋白在“高炎症”精神分裂症中升高,而 ICAM1 mRNA 在白细胞中没有变化。与对照组相比,精神分裂症患者的白细胞中 LFA1 mRNA 减少,CR3 mRNA 增加。LFA1 mRNA水平与工作记忆呈正相关,可溶性ICAM1升高与精神分裂症的言语记忆呈负相关。总之,精神分裂症中的一些认知缺陷可能与调节免疫细胞运输的分子表达改变有关。因此,通过诊断和炎症亚组分析基因表达。与“高”和“低炎症”对照相比,先前测量的血浆 ICAM1 蛋白在“高炎症”精神分裂症中升高,而 ICAM1 mRNA 在白细胞中没有变化。与对照组相比,精神分裂症患者的白细胞中 LFA1 mRNA 减少,CR3 mRNA 增加。LFA1 mRNA水平与工作记忆呈正相关,可溶性ICAM1升高与精神分裂症的言语记忆呈负相关。总之,精神分裂症中的一些认知缺陷可能与调节免疫细胞运输的分子表达改变有关。因此,通过诊断和炎症亚组分析基因表达。与“高”和“低炎症”对照相比,先前测量的血浆 ICAM1 蛋白在“高炎症”精神分裂症中升高,而 ICAM1 mRNA 在白细胞中没有变化。与对照组相比,精神分裂症患者的白细胞中 LFA1 mRNA 减少,CR3 mRNA 增加。LFA1 mRNA水平与工作记忆呈正相关,可溶性ICAM1升高与精神分裂症的言语记忆呈负相关。总之,精神分裂症中的一些认知缺陷可能与调节免疫细胞运输的分子表达改变有关。与“高”和“低炎症”对照相比,先前测量的血浆 ICAM1 蛋白在“高炎症”精神分裂症中升高,而 ICAM1 mRNA 在白细胞中没有变化。与对照组相比,精神分裂症患者的白细胞中 LFA1 mRNA 减少,CR3 mRNA 增加。LFA1 mRNA水平与工作记忆呈正相关,可溶性ICAM1升高与精神分裂症的言语记忆呈负相关。总之,精神分裂症中的一些认知缺陷可能与调节免疫细胞运输的分子表达改变有关。与“高”和“低炎症”对照相比,先前测量的血浆 ICAM1 蛋白在“高炎症”精神分裂症中升高,而 ICAM1 mRNA 在白细胞中没有变化。与对照组相比,精神分裂症患者的白细胞中 LFA1 mRNA 减少,CR3 mRNA 增加。LFA1 mRNA水平与工作记忆呈正相关,可溶性ICAM1升高与精神分裂症的言语记忆呈负相关。总之,精神分裂症中的一些认知缺陷可能与调节免疫细胞运输的分子表达改变有关。与对照组相比,精神分裂症患者的白细胞中 LFA1 mRNA 减少,CR3 mRNA 增加。LFA1 mRNA水平与工作记忆呈正相关,可溶性ICAM1升高与精神分裂症的言语记忆呈负相关。总之,精神分裂症中的一些认知缺陷可能与调节免疫细胞运输的分子表达改变有关。与对照组相比,精神分裂症患者的白细胞中 LFA1 mRNA 减少,CR3 mRNA 增加。LFA1 mRNA水平与工作记忆呈正相关,可溶性ICAM1升高与精神分裂症的言语记忆呈负相关。总之,精神分裂症中的一些认知缺陷可能与调节免疫细胞运输的分子表达改变有关。
更新日期:2020-10-01
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