{"id":34615,"date":"2022-05-23T19:30:12","date_gmt":"2022-05-23T11:30:12","guid":{"rendered":"https:\/\/swarma.org\/?p=34615"},"modified":"2022-05-23T19:30:12","modified_gmt":"2022-05-23T11:30:12","slug":"nature%e9%80%9f%e9%80%92%ef%bc%9a%e5%b9%b4%e8%bd%bb%e5%b0%8f%e9%bc%a0%e8%84%91%e8%84%8a%e6%b6%b2%e6%94%b9%e5%96%84%e8%80%81%e5%b9%b4%e5%b0%8f%e9%bc%a0%e8%ae%b0%e5%bf%86","status":"publish","type":"post","link":"https:\/\/swarma.org\/?p=34615","title":{"rendered":"Nature\u901f\u9012\uff1a\u5e74\u8f7b\u5c0f\u9f20\u8111\u810a\u6db2\u6539\u5584\u8001\u5e74\u5c0f\u9f20\u8bb0\u5fc6"},"content":{"rendered":"
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\u57fa\u4e8e\u5bf9\u5faa\u73af\u7cfb\u7edf\u73af\u5883\u5982\u4f55\u5728\u751f\u547d\u5386\u7a0b\u4e2d\u5f71\u54cd\u5927\u8111\u7684\u7406\u89e3\uff0c\u6700\u8fd1\u51fa\u73b0\u4e86\u8bb8\u591a\u5ef6\u7f13\u5927\u8111\u8870\u8001\u7684\u5e72\u9884\u63aa\u65bd\u3002\u63d0\u4f9b\u8425\u517b\u7269\u8d28\u7684\u8111\u810a\u6db2\uff08Cerebrospinal Fluid, CSF\uff09\u662f\u8111\u7ec6\u80de\u7684\u76f4\u63a5\u73af\u5883\u3002\u7814\u7a76\u8005\u53d1\u73b0\u5c06\u5e74\u8f7b\u5c0f\u9f20\u7684\u8111\u810a\u6db2\u76f4\u63a5\u6ce8\u5165\u5e74\u8001\u5c0f\u9f20\u7684\u5927\u8111\u53ef\u4ee5\u6539\u5584\u5176\u8bb0\u5fc6\u529f\u80fd\u3002\u901a\u8fc7\u6d77\u9a6c\u7684\u65e0\u504f\u6027\u8f6c\u5f55\u7ec4\u5206\u6790\uff08unbiased transcriptome analysis\uff09\u53d1\u73b0\uff0c\u5c11\u7a81\u80f6\u8d28\u7ec6\u80de\u5bf9\u8fd9\u79cd\u6062\u590d\u9752\u6625\u7684\u8111\u810a\u6db2\u73af\u5883\u6700\u654f\u611f\u3002<\/span><\/strong><\/p>\n


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\u672c\u7814\u7a76\u8fdb\u4e00\u6b65\u8bc1\u660e\uff0c\u5e74\u8f7b\u8111\u810a\u6db2\u80fd\u4fc3\u8fdb\u8001\u5e74\u6d77\u9a6c\u548c\u539f\u4ee3\u57f9\u517b\u4e2d\u7684\u5c11\u7a81\u80f6\u8d28\u7ec6\u80de\u7956\u7ec6\u80de\uff08Oligodendrocyte Progenitor Cell, OPC\uff09\u7684\u589e\u6b96\u548c\u5206\u5316\u3002\u5229\u7528SLAMseq*\u5bf9\u65b0\u751fmRNA\u8fdb\u884c\u4ee3\u8c22\u6807\u8bb0\uff0c\u7814\u7a76\u8005\u786e\u5b9a\u4e86\u4e00\u79cd\u9a71\u52a8\u808c\u52a8\u86cb\u767d\u7ec6\u80de\u9aa8\u67b6\u91cd\u6392\u7684\u8f6c\u5f55\u56e0\u5b50\u2014\u2014\u8840\u6e05\u53cd\u5e94\u56e0\u5b50\uff08Serum Response Factor, SRF\uff09\u662f\u66b4\u9732\u4e8e\u5e74\u8f7b\u8111\u810a\u6db2\u4e2dOPC\u589e\u6b96\u7684\u4e2d\u4ecb\u3002\u5728\u6d77\u9a6cOPC\u4e2d\uff0cSRF\u968f\u7740\u5e74\u9f84\u589e\u957f\u800c\u8868\u8fbe\u4e0b\u964d\uff0c\u901a\u8fc7\u5e74\u8f7b\u8111\u810a\u6db2\u7684\u6025\u6027\u6ce8\u5c04\u8bf1\u5bfc\u4e86\u8be5\u9014\u5f84\u3002<\/strong><\/section>\n

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*\u8bd1\u6ce8\uff1aSLAM-seq\uff08High-Throughput Metabolic Sequencing of RNA\uff09\u662f\u4e00\u79cd\u57fa\u4e8e\u5def\u57fa\uff08SH\uff09\u70f7\u57fa\u5316\u7684RNA\u4ee3\u8c22\u6d4b\u5e8f\u65b9\u6cd5\uff0c\u5e76\u4e14\u4e0d\u9700\u8981\u751f\u5316\u5206\u79bb\u6280\u672f\u8f85\u52a9\uff0c\u56e0\u6b64\u53ef\u4ee5\u65b9\u4fbf\u5730\u89e3\u51b3\u66f4\u6df1\u5c42\u6b21\u7684\u3001\u51b3\u5b9a\u6574\u4f53\u7a33\u6001\u6c34\u5e73\u7684RNA\u8f6c\u5f55\u4e0e\u964d\u89e3\u7684\u57fa\u672c\u52a8\u529b\u5b66\u95ee\u9898\u3002<\/span><\/section>\n


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\u8bba\u6587\u9898\u76ee<\/span>\uff1a<\/span><\/p>\n

Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17<\/span><\/p>\n

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\u53d1\u8868\u4e8e Nature<\/em> \u7684\u6700\u65b0\u7814\u7a76\u5728\u5927\u8111\u5065\u5eb7\u548c\u8870\u8001\u9886\u57df\u53d6\u5f97\u4e86\u7a81\u7834\uff0c\u53d1\u73b0\u5e74\u8f7b\u8111\u810a\u6db2\u4e2d\u542b\u6709\u4e00\u79cd\u901a\u8fc7\u5c11\u7a81\u80f6\u8d28\u7ec6\u80de\u6210\u719f\u548c\u6d77\u9a6c\u9ad3\u9798\u5f62\u6210\u6765\u5e2e\u52a9\u8001\u5e74\u5c0f\u9f20\u8bb0\u5fc6\u56de\u5fc6\u7684\u56e0\u5b50\u3002\u672c\u7814\u7a76\u7ed3\u5408\u4e86\u884c\u4e3a\u5b66\u3001\u7ec4\u5b66\u7b49\u591a\u79cd\u5b9e\u9a8c\u65b9\u6cd5\uff0c\u5177\u4f53\u5305\u62ec\u4e86\u5b66\u4e60\u4e0e\u8bb0\u5fc6\u80fd\u529b\u6d4b\u8bd5\u3001\u6d77\u9a6c\u7ec6\u80deRNAseq\u548c\u7ec4\u5b66\u5206\u6790\uff0c\u591a\u79cd\u5c42\u9762\u9a8c\u8bc1\u5e74\u8f7b\u8111\u810a\u6db2\u53ef\u4ee5\u6539\u5584\u8001\u5e74\u5927\u8111\u8bb0\u5fc6\uff0c\u5982\u56fe2\u6240\u793a\u3002<\/span><\/section>\n
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  1. \n
    Pluvinage, J. V. & Wyss-Coray, T. Systemic factors as mediators of brain homeostasis, ageing and neurodegeneration. Nat. Rev. Neurosci. 21, 93\u2013102 (2020).<\/span><\/section>\n<\/li>\n
  2. \n
    Villeda, S. A. et al. Nature 477, 90\u201394 (2011).<\/span><\/section>\n<\/li>\n
  3. \n
    Villeda, S. A. et al. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat. Med. 20, 659\u2013663 (2014).<\/span><\/section>\n<\/li>\n
  4. \n
    Fame, R. M. & Lehtinen, M. K. Emergence and developmental roles of the cerebrospinal fluid system. Dev. Cell 52, 261\u2013275 (2020).<\/span><\/section>\n<\/li>\n
  5. \n
    Chen, C. P., Chen, R. L. & Preston, J. E. The influence of ageing in the cerebrospinal fluid concentrations of proteins that are derived from the choroid plexus, brain, and plasma. Exp. Gerontol. 47, 323\u2013328 (2012).<\/span><\/section>\n<\/li>\n
  6. \n
    Baird, G. S. et al. Age-dependent changes in the cerebrospinal fluid proteome by slow off-rate modified aptamer array. Am. J. Pathol. 180, 446\u2013456 (2012).<\/span><\/section>\n<\/li>\n
  7. \n
    Islam, M. R. et al. Nature Metab. 3, 1058\u20131070 (2021).<\/span><\/section>\n<\/li>\n
  8. \n
    Lehtinen, M. K. et al. Neuron 69, 893\u2013905 (2011).<\/span><\/section>\n<\/li>\n
  9. \n
    Fame, R. M. & Lehtinen, M. K. Dev. Cell 52, 261\u2013275 (2020).<\/span><\/section>\n<\/li>\n
  10. \n

    https:\/\/www.nature.com\/articles\/d41586-022-00860-7#ref-CR6<\/span><\/p>\n<\/li>\n<\/ol>\n<\/section>\n

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    \u8bba\u6587 Abstract<\/strong><\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

    Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies to slow brain ageing. Cerebrospinal fluid (CSF) makes up the immediate environment of brain cells, providing them with nourishing compounds. We discovered that infusing young CSF directly into aged brains improves memory function. Unbiased transcriptome analysis of the hippocampus identified oligodendrocytes to be most responsive to this rejuvenated CSF environment. We further showed that young CSF boosts oligodendrocyte progenitor cell (OPC) proliferation and differentiation in the aged hippocampus and in primary OPC cultures. Using SLAMseq to metabolically label nascent mRNA, we identified serum response factor (SRF), a transcription factor that drives actin cytoskeleton rearrangement, as a mediator of OPC proliferation following exposure to young CSF. With age, SRF expression decreases in hippocampal OPCs, and the pathway is induced by acute injection with young CSF. We screened for potential SRF activators in CSF and found that fibroblast growth factor 17 (Fgf17) infusion is sufficient to induce OPC proliferation and long-term memory consolidation in aged mice while Fgf17 blockade impairs cognition in young mice. These findings demonstrate the rejuvenating power of young CSF and identify Fgf17 as a key target to restore oligodendrocyte function in the ageing brain.<\/span><\/section>\n

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