Neural Stem Cell Dysfunction in Delayed Radiation Injury

描述（由申请人提供）：颅脑放射治疗的一个常见且使人衰弱的副作用是永久性和持续的认知能力下降，包括学习和记忆受损。尽管先前的研究表明，这种缺陷会改变海马功能，但我们首次发现颅脑放射损伤成体神经干细胞，破坏海马神经发生，并永久性地破坏海马微环境，使其无法支持神经发生。即使在未辐照的干细胞重建后，受辐照的海马亚颗粒区显示出两个重要的长期改变，这可能是其无法支持神经发生的原因：正常神经干细胞活性的丧失和“神经血管生成”微环境的破坏。

DESCRIPTION (provided by applicant): A common and debilitating side effect of cranial radiation therapy is a permanent and continually progressive decline in cognition that includes impaired learning and memory, Although previous work has implicated altered hippocampal function in this deficit, we show for the first time that cranial radiation injures adult neural stem cells, ablates hippocampal neurogenesis and permanently disrupts the hippocampal microenvironment making it unable to support neurogenesis, even following reconstitution with non-irradiated stem cells, The irradiated hippocampal subgranule zone displays two important long-term alterations that may account for its inability to support neurogenesis: a loss of normal neural stem cell activity and disruption of the "neuro-angiogenic" microenvironment. The proposed experiments further characterize the radiation sensitivity of adult neural stem cells and explore the potential utility of radio-protective as well as reconstitution strategies to reduce the impact of radiation on neurogenesis in the adult brain.