Functional roles of astrocytes in modulating neural stem and progenitor cells in the adult mammalian spinal cord

星形胶质细胞在调节成年哺乳动物脊髓神经干细胞和祖细胞中的功能作用

• 批准号: 418578-2012
• 负责人: Karimi, Soheila
• 金额: $ 2.4万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=573724
• 关键词: Functional; roles; astrocytes; modulating; neural

Adult mammalian spinal cord lacks the ability for self repair despite the presence of tissue-specific neural stem cells (NSCs) inside the spinal cord. During the developmental growth, NSCs show the capacity to give rise to all types of spinal cord cells including neurons, astrocytes and oligodendrocytes and build the spinal cord. However, in the adult spinal cord, the regenerative activity of NSCs is significantly restricted. Interestingly, evidence from our research and that of others demonstrates that injuries to the adult spinal cord result in limited oligodendroglial cell replacement, a glial cell type required for generating myelin sheath around the spinal cord nerve fibers. These findings strongly suggest the presence of environmental factors that tightly regulate the innate potential of NSCs within the adult spinal cord. To date, we have only a poor understanding of the events that modulate the properties of adult NSCs within their spinal cord environment. Our goal is to understand the dynamic responses of spinal cord NSCs to changing their environment under both normal and disease conditions. In this proposal, my team and I will focus on the impact of astrocytes and their secreted factors in controlling the properties of endogenous NSCs in the developing and adult spinal cord. Astrocytes are support cells of the spinal cord that play pivotal roles in many aspects of spinal cord biology. Astrocytes secrete a host of cytokines and growth factors with both promoting and inhibitory nature that can influence the behaviour of NSCs. The knowledge to be gained from this research will provide new fundamental knowledge in spinal cord research and novel targets for enhancing endogenous repair and regeneration in conditions such as spinal cord injuries and multiple sclerosis. Importantly, this research program will also provide a unique opportunity for undergraduate and graduate students as well as junior researcher to gain highly valued expertise in neuroscience and stem cell research and to develop the skills to perform independent scientific research.

成年哺乳动物脊髓缺乏自我修复能力，尽管脊髓内存在组织特异性神经干细胞（NSCs）。在发育生长过程中，NSCs显示出产生包括神经元、星形胶质细胞和少突胶质细胞在内的所有类型脊髓细胞并构建脊髓的能力。然而，在成人脊髓中，NSCs的再生活性明显受到限制。有趣的是，来自我们和其他研究的证据表明，成人脊髓损伤导致有限的少突胶质细胞替代，这是脊髓神经纤维周围产生髓鞘所需的胶质细胞类型。这些发现有力地表明，存在严格调节成人脊髓内NSCs先天潜能的环境因素。