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Nat Med:日本学者找到中枢神经再生方法

摘要 : 2017年6月19日,国际学术权威刊物自然出版集团旗下子刊《Nature Medicine》杂志在线发表了日本九州大学Seiji Okada研究员的一篇研究论文,研究发现了抑制哺乳动物中枢神经细胞再生的主要原因,以及克服这一障碍让中枢神经细胞再生的方法

2017年6月19日,国际学术权威刊物自然出版集团旗下子刊《Nature Medicine》杂志在线发表了日本九州大学Seiji Okada研究员的一篇研究论文,研究发现了抑制哺乳动物中枢神经细胞再生的主要原因,以及克服这一障碍让中枢神经细胞再生的方法,研究成果将有助于脊髓损伤的治疗。

研究指出,手脚等处的末梢神经即使受损也会慢慢再生,而脑和脊髓等部位的中枢神经几乎不会再生。脑梗塞和脊髓损伤后往往留下身体麻痹等重度后遗症,其重要原因是,中枢神经受损部位附近的星形胶质细胞会形成名为胶质瘢痕的结痂状组织,阻碍中枢神经细胞再生。

该校一个研究小组利用实验鼠进行了脊髓损伤实验,在脊髓损伤部位发现了一种具有黏着细胞功能的“I型胶原蛋白”。这种蛋白质数量异常多,可能和胶质瘢痕的形成有关。研究人员向实验鼠脊髓注射了抑制这种蛋白质作用的抗体,结果发现,胶质瘢痕的形成受到了抑制,实验鼠中枢神经得以再生,麻痹症状也得以减轻。

研究人员称,虽然近年来诱导多能干细胞(iPS细胞)等技术在中枢神经再生治疗中广受期待,但对于已经形成胶质瘢痕的患者,即使移植干细胞,胶质瘢痕也会影响神经细胞再生。新发现有望帮助改善干细胞移植的治疗效果。

原文链接:

Interaction of reactive astrocytes with type I collagen induces astrocytic scar formation through the integrin–N-cadherin pathway after spinal cord injury

原文摘要:

Central nervous system (CNS) injury transforms naive astrocytes into reactive astrocytes, which eventually become scar-forming astrocytes that can impair axonal regeneration and functional recovery. This sequential phenotypic change, known as reactive astrogliosis, has long been considered unidirectional and irreversible. However, we report here that reactive astrocytes isolated from injured spinal cord reverted in retrograde to naive astrocytes when transplanted into a naive spinal cord, wheras they formed astrocytic scars when transplanted into injured spinal cord, indicating the environment-dependent plasticity of reactive astrogliosis. We also found that type I collagen was highly expressed in the spinal cord during the scar-forming phase and induced astrocytic scar formation via the integrin–N-cadherin pathway. In a mouse model of spinal cord injury, pharmacological blockade of reactive astrocyte–type I collagen interaction prevented astrocytic scar formation, thereby leading to improved axonal regrowth and better functional outcomes. Our findings reveal environmental cues regulating astrocytic fate decisions, thereby providing a potential therapeutic target for CNS injury.

来源: Nature Medicine 浏览次数:0

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