小柯机器人

美国斯坦福大学Tony Wyss-Coray、Tal Iram等研究人员合作发现，年轻的脑脊液（CSF）通过Fgf17恢复老年小鼠的少突胶质生成和记忆力。2022年5月11日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员发现，将年轻的CSF直接注入老年大脑可改善记忆功能。对海马的无偏倚转录组分析表明，少突胶质细胞对这种年轻的CSF环境反应最为强烈。结果进一步表明，年轻的CSF能促进少突胶质细胞祖细胞（OPC）在老年海马和初级OPC培养物中的增殖和分化。利用SLAMseq对新生的mRNA进行代谢标记，研究人员确定了血清反应因子（SRF），一种驱动肌动蛋白细胞骨架重排的转录因子，是暴露于年轻CSF后OPC增殖的一个媒介。随着年龄的增长，SRF在海马OPC中的表达减少，而该途径被急性注射年轻CSF所诱导。

研究人员筛选了CSF中潜在的SRF激活剂，并发现成纤维细胞生长因子17（Fgf17）的注入足以诱导OPC增殖和老年小鼠的长期记忆巩固，而Fgf17的阻断会损害年轻小鼠的认知能力。这些发现证明了年轻CSF的再生能力，并确定Fgf17是恢复衰老大脑中少突胶质细胞功能的一个关键靶标。

据了解，最近，人们对系统环境如何在整个生命过程中塑造大脑的认识，导致了许多干预策略，用于减缓大脑的老化。CSF构成了脑细胞的直接环境，为它们提供了滋养的化合物。

附：英文原文

Title: Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17

Author: Iram, Tal, Kern, Fabian, Kaur, Achint, Myneni, Saket, Morningstar, Allison R., Shin, Heather, Garcia, Miguel A., Yerra, Lakshmi, Palovics, Robert, Yang, Andrew C., Hahn, Oliver, Lu, Nannan, Shuken, Steven R., Haney, Michael S., Lehallier, Benoit, Iyer, Manasi, Luo, Jian, Zetterberg, Henrik, Keller, Andreas, Zuchero, J. Bradley, Wyss-Coray, Tony

Issue&Volume: 2022-05-11

Abstract: Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies to slow brain ageing1,2,3. Cerebrospinal fluid (CSF) makes up the immediate environment of brain cells, providing them with nourishing compounds4,5. 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.

DOI: 10.1038/s41586-022-04722-0

Source: https://www.nature.com/articles/s41586-022-04722-0

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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