期刊
BRAIN
卷 137, 期 -, 页码 2312-2328出版社
OXFORD UNIV PRESS
DOI: 10.1093/brain/awu155
关键词
neural stem cells; adult neurogenesis; Alzheimer's disease; variant CJD
资金
- European Union [IEF273243]
- MEC (Spain)
- MRC [MR/K022687/1]
- DFG [SFB841]
- Medical Research Council [MR/K022687/1] Funding Source: researchfish
- MRC [MR/K022687/1] Funding Source: UKRI
Increased neurogenesis has been reported in neurodegenerative disease, but its significance is unclear. In a mouse model of prion disease, Gomez-Nicola et al. detect increased neurogenesis in the dentate gyrus that partially counteracts neuronal loss. Targeting neurogenesis may have therapeutic potential.The study of neurogenesis during chronic neurodegeneration is crucial in order to understand the intrinsic repair mechanisms of the brain, and key to designing therapeutic strategies. In this study, using an experimental model of progressive chronic neurodegeneration, murine prion disease, we define the temporal dynamics of the generation, maturation and integration of new neurons in the hippocampal dentate gyrus, using dual pulse-chase, multicolour gamma-retroviral tracing, transmission electron microscopy and patch-clamp. We found increased neurogenesis during the progression of prion disease, which partially counteracts the effects of chronic neurodegeneration, as evidenced by blocking neurogenesis with cytosine arabinoside, and helps to preserve the hippocampal function. Evidence obtained from human post-mortem samples, of both variant Creutzfeldt-Jakob disease and Alzheimer's disease patients, also suggests increased neurogenic activity. These results open a new avenue into the exploration of the effects and regulation of neurogenesis during chronic neurodegeneration, and offer a new model to reproduce the changes observed in human neurodegenerative diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据