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首页> 外文期刊>Neuropathology and applied neurobiology >PICK1 expression in reactive astrocytes within the spinal cord of amyotrophic lateral sclerosis (ALS) rats
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PICK1 expression in reactive astrocytes within the spinal cord of amyotrophic lateral sclerosis (ALS) rats

机译:肌萎缩性侧索硬化症(ALS)大鼠脊髓内反应性星形胶质细胞中PICK1表达

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Aims: The protein interacting with C kinase 1 (PICK1), a PDZ domain-containing protein mainly expressed in the central nervous system, interacts with the glutamate receptor subunit GluR2, with the glutamate transporter GLT-1b and with the enzyme serine racemase. These three proteins appear as key actors in the glutamate-mediated excitotoxicity associated with amyotrophic lateral sclerosis (ALS), in both patients and animal models of the disease. In this study, we examined the expression of PICK1 in the spinal cord of transgenic rats expressing a mutated form of the human superoxide dismutase 1 (hSOD1G93A) during the progression of the disease. Methods: Expression of PICK1 was examined by real-time qPCR at presymptomatic and symptomatic stages as well as at end-stage. The expression of PICK1 in the different cell types of the spinal cord was examined by immunohistochemistry. Results: The overall expression of PICK1 is not modified in cervical and lumbar spinal cord of transgenic (hSOD1G93A) rats during the progression of the disease. Nonetheless, immunohistochemical studies of lumbar ventral horns revealed a shift of PICK1 expression from motor neurones in healthy rats to activated astrocytes in end-stage hSOD1G93A animals. Conclusions: Considering the documented influence of PICK1 expression on d-serine release and glutamate transport in astrocytes, these findings point to a potential implication of PICK1 in the progression of ALS.
机译:目的:该蛋白与C激酶1(PICK1)相互作用,该蛋白主要在中枢神经系统中表达,是一个包含PDZ域的蛋白,它与谷氨酸受体亚基GluR2,谷氨酸转运蛋白GLT-1b和丝氨酸消旋酶相互作用。在该疾病的患者和动物模型中,这三种蛋白质均是与肌萎缩性侧索硬化症(ALS)相关的谷氨酸介导的兴奋性毒性的关键因子。在这项研究中,我们检查了在疾病发展过程中表达突变型人类超氧化物歧化酶1(hSOD1G93A)的转基因大鼠脊髓中PICK1的表达。方法:通过实时qPCR在症状前和症状期以及末期检测PICK1的表达。通过免疫组织化学检查了PICK1在脊髓的不同细胞类型中的表达。结果:在疾病进展过程中,转基因(hSOD1G93A)大鼠的颈腰椎脊髓中PICK1的总体表达未发生改变。尽管如此,腰腹角的免疫组织化学研究显示健康大鼠的PICK1表达从运动神经元转移到了hSOD1G93A晚期动物的活化星形胶质细胞。结论:考虑到PICK1表达对星形胶质细胞中d-丝氨酸释放和谷氨酸转运的影响,这些发现表明PICK1对ALS的发展具有潜在的影响。

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