Immunofluorescent labeling of increased calpain expression and neuronal death in the spinal cord of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice
Immunofluorescent labeling of increased calpain expression and neuronal death in the spinal cord of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice
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DOI：
10.1016/j.brainres.2004.01.065
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发表时间：
2004-05-01
期刊：
影响因子：
2.9
通讯作者：
Banik, NL
中科院分区：
文献类型：
--
作者：
Chera, H;Schaecher, KE;Banik, NL
帕金森病（PD）是一种以强直、震颤和运动迟缓为特征的运动障碍，起源于黑质（SN）、红核后区和蓝斑（LC）的多巴胺能神经元变性。钙蛋白酶与神经退行性疾病的病理生理学有关。由于脊髓 (SC) 和大脑是紧密相连的，并且钙蛋白酶参与细胞死亡和线粒体功能障碍，因此我们假设 SC 神经元也在 PD 中受到影响。为了检验这一假设，我们检查了经过 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 处理的小鼠的大脑和 SC。为了鉴定表达钙蛋白酶的细胞，使用钙蛋白酶特异性抗体和细胞类型（OX-42、GFAP 或 NeuN）进行双重免疫荧光标记。结合末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记 (TUNEL) 和双重免疫荧光标记用于识别中枢神经系统 (CNS) 中特定细胞的死亡。与对照组相比，第 1 天和第 7 天，MPTP 治疗小鼠 SC 中的小胶质细胞、星形胶质细胞和神经元中的钙蛋白酶表达有所增加。 SC 和 SN 中的 TUNEL 阳性神经元表现出凋亡特征。这些结果表明，MPTP 治疗小鼠的神经元死亡不仅发生在 SN 中，而且也发生在 SC 中，并为 MPTP 诱导的小鼠帕金森症中可能存在钙蛋白酶介导的 SC 神经元死亡提供了证据。 (C) 2004 Elsevier B.V. 保留所有权利。
Parkinson's disease (PD) is a movement disorder characterized by rigidity, tremor, and bradykinesia, originating from degeneration of dopaminergic neurons in the substantia nigra (SN), retrorubral area, and locus ceoruleus (LC). Calpain has been implicated in the pathophysiology of neurodegenerative diseases. Since the spinal cord (SC) and brain are integrally connected and calpain is involved in cell death and mitochondrial dysfunction, we hypothesized that SC neurons are also affected in PD. In order to examine this hypothesis, we examined both brain and SC from mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To identify cells expressing calpain, double immunofluorescent labeling was performed with antibodies specific for calpain and a cell type (OX-42, GFAP, or NeuN). Combined terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and double immunofluorescent labeling were used to identify death of specific cells in the central nervous system (CNS). There was an increase in calpain expression in microglia, astrocytes, and neurons in the SC of MPTP-treated mice at 1 and 7 days, as compared to controls. TUNEL-positive neurons in the SC and SN showed apoptotic characteristics. These results demonstrated that neuronal death occurred not only in SN but also in the SC of MPTP-treated mice and has provided evidence for a possible calpain-mediated SC neuronal death in MPTP-induced parkinsonism in mice. (C) 2004 Elsevier B.V. All rights reserved.