NEUROMUSCULAR AND CENTRAL NERVOUS SYSTEM DISEASES AND THEIR EXPERIMENTAL MODELS

神经肌肉和中枢神经系统疾病及其实验模型

• 批准号: 3782336
• 负责人: M C DALAKAS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3782336
• 关键词: HIV infections; Primates; Retroviridae; autoimmune disorder; biopsy; carnitine; dermatomyositis; disease /disorder model; drug adverse effect; histocompatibility antigens; human immunodeficiency virus; human subject; human tissue; immunopathology diagnosis; laboratory rat; muscular dystrophy; myelinopathy; nervous system disorder diagnosis; neural cell adhesion molecules; neuromuscular disorder; poliomyelitis; polymyositis; simian immunodeficiency virus; virus receptors; zidovudine

The Section runs the Laboratory of Muscle Enzyme Histochemistry that processes up to 300 muscle and nerve biopsies per year for diagnostic studies. Examined muscle specimens are from patients with neuromuscular manifestations related to systemic autoimmune, viral, metabolic, endocrine or infectious diseases, and from patients with primary neuromuscular disorders, such as polymyositis, dermatomyositis, neurogenic muscular atrophies, muscular dystrophies, post-polio syndrome, mitochondrial encephalomyopathies and biochemical or genetic muscle diseases such as central core disease or hypertrophic cardiomyopathy. The laboratory is also involved in the following immunologic, biochemic and virologic studies that examine the susceptibility of the muscle and nerve to immune or viral mediated injuries: (a) Study the regeneration of human muscle in health and disease and the maturation of satellite cells by examining the expression of neural cell adhesion molecules and laminins; (b) study the susceptibility of muscle and nerve to infection with retroviruses and the ability of HIV or HIV-infected lymphoid cells to infect human myotubes in culture and induce expression of MHC-antigens; (c) study the expression of the poliovirus receptor in human muscle and the ability of the poliovirus to infect and replicate in human myotubes; (d) study the effects of cytokines and lymphokines on human muscle myotubes and examine the role of LCAM-L in enhancing myocytotoxicity by promoting the adhesion of cytotoxic T cells to myotubes; (e) study the toxicity of AZT to muscle mitochondria by applying AZT to human muscle in culture; (f) study the effect of L- carnitine in reversing the mitochondrial abnormalities induced by AZT on myotubes and (g) use animal models to study: i) the pathogenesis of retrovirus-induced inflammatory myopathy by examining muscles from monkeys infected with the simian immunodeficiency virus; ii) the mechanism of AZT- induced mitochondrial myopathy by examining the structural, metabolic and functional alterations in the muscle mitochondria of healthy rats injected with AZT; and iii) the effect of L-carnitine in reversing or improving the AZT-induced myopathy in the rats.

该科负责管理肌肉酶组织化学实验室 每年处理多达 300 个肌肉和神经活检用于诊断 研究。 检查的肌肉标本来自患有神经肌肉疾病的患者 与全身自身免疫、病毒、代谢、内分泌相关的表现 或传染病，以及患有原发性神经肌肉疾病的患者 疾病，如多发性肌炎、皮肌炎、神经源性肌肉炎 萎缩、肌营养不良、脊髓灰质炎后综合症、线粒体 脑肌病和生化或遗传性肌肉疾病，例如 中央核心疾病或肥厚性心肌病。 该实验室是 还涉及以下免疫学、生物化学和病毒学 检查肌肉和神经对免疫的敏感性的研究 或病毒介导的损伤：(a) 研究人体肌肉的再生 通过检查健康和疾病以及卫星细胞的成熟 神经细胞粘附分子和层粘连蛋白的表达； (b) 研究 肌肉和神经对逆转录病毒感染的易感性和 HIV或HIV感染的淋巴细胞感染人类肌管的能力 培养并诱导 MHC 抗原的表达； (c) 研究表达 人体肌肉中的脊髓灰质炎病毒受体和脊髓灰质炎病毒的能力 感染人类肌管并在其中复制； (d) 研究影响 细胞因子和淋巴因子对人体肌肉肌管的作用并检查 LCAM-L 通过促进细胞毒性物质的粘附来增强肌细胞毒性 T细胞到肌管； (e) 研究AZT对肌肉线粒体的毒性 将 AZT 应用于培养的人体肌肉； (f) 研究L-的影响 肉碱逆转 AZT 诱导的线粒体异常 肌管和（g）使用动物模型来研究：i）发病机制 通过检查猴子的肌肉来发现逆转录病毒诱导的炎症性肌病 感染猿猴免疫缺陷病毒； ii) AZT 的机制- 通过检查结构、代谢和诱导线粒体肌病 注射健康大鼠肌肉线粒体的功能改变 与 AZT 一起使用； iii) 左旋肉碱在逆转或改善 AZT 诱导的大鼠肌病。