年轻系统因素对衰老小鼠大脑的血管和神经再生作用。
Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors.
机构信息
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
出版信息
Science. 2014 May 9;344(6184):630-4. doi: 10.1126/science.1251141. Epub 2014 May 5.
Abstract
In the adult central nervous system, the vasculature of the neurogenic niche regulates neural stem cell behavior by providing circulating and secreted factors. Age-related decline of neurogenesis and cognitive function is associated with reduced blood flow and decreased numbers of neural stem cells. Therefore, restoring the functionality of the niche should counteract some of the negative effects of aging. We show that factors found in young blood induce vascular remodeling, culminating in increased neurogenesis and improved olfactory discrimination in aging mice. Further, we show that GDF11 alone can improve the cerebral vasculature and enhance neurogenesis. The identification of factors that slow the age-dependent deterioration of the neurogenic niche in mice may constitute the basis for new methods of treating age-related neurodegenerative and neurovascular diseases.
摘要
在成人中枢神经系统中，神经发生龛的脉管系统通过提供循环和分泌因子来调节神经干细胞的行为。与神经发生和认知功能下降相关的是，随着年龄的增长，血流量减少和神经干细胞数量减少。因此，恢复龛的功能应该可以抵消衰老的一些负面影响。我们发现，年轻血液中的因子可诱导血管重塑，最终导致衰老小鼠的神经发生增加和嗅觉辨别力提高。此外，我们还发现，GDF11 本身就可以改善大脑血管并增强神经发生。鉴定出可减缓小鼠神经发生龛随年龄增长而恶化的因子，可能为治疗与年龄相关的神经退行性和神经血管疾病的新方法奠定基础。
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2
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Nat Neurosci. 2013 Sep;16(9):1211-1218. doi: 10.1038/nn.3469. Epub 2013 Jul 21.
3
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Cell. 2013 May 9;153(4):828-39. doi: 10.1016/j.cell.2013.04.015.
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J Cereb Blood Flow Metab. 2013 Jan;33(1):146-56. doi: 10.1038/jcbfm.2012.152. Epub 2012 Oct 24.
5
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Cell Stem Cell. 2012 Jan 6;10(1):96-103. doi: 10.1016/j.stem.2011.11.019.
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7
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