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Iram T, Kern F, Kaur A, Myneni S, Morningstar AR, Shin H, Garcia MA, Yerra L, Palovics R, Yang AC, Hahn O, Lu N, Shuken SR, Haney MS, Lehallier B, Iyer M, Luo J, Zetterberg H, Keller A, Zuchero JB, Wyss-Coray T. Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17. Nature. 2022 May;605(7910):509-515. Epub 2022 May 11 PubMed. Correction.
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University of Pittsburgh
I very much enjoyed reading this outstanding paper from the Wyss-Coray lab. The discovery that infusing young CSF into aged brains improves memory function and boosts OPC proliferation and differentiation is fascinating and a very important contribution. This work demonstrates the rejuvenating capacity of young CSF and highlights oligodendrocyte lineage cells as a potential target for therapeutic strategies to prevent age-associated cognitive decline.
View all comments by Hansruedi MathysMIT
Picower Institute of MIT
In this exciting paper from Tony Wyss-Coray's group at Stanford, researchers lead by Dr. Tal Iram found that cerebrospinal fluid isolated from young mice stimulates oligodendrocyte precursor proliferation and differentiation, and promotes myelination in aged mice. Infusion of "young" CSF into aged mice also improved learning in a contextual memory paradigm. Interestingly, the transcription factor Serum Response Factor (SRF), and the growth factor Fgf17, were identified as putative mediators of these effects.
This important study adds to a growing body of literature highlighting oligodendrocyte lineage cells as active contributors to brain function, and potential drivers of disease. Understanding how SRF and Fgf17 promote myelination, and determining whether this can be leveraged to treat neurodegenerative diseases associated with demyelination and white-matter injury, will make for exciting future research.
View all comments by Li-Huei TsaiThird Military Medical University
Oligodendrogenesis: A Brake on Brain Aging?
Interventions to slow down cognitive decline are sorely needed for the increasing elderly population worldwide. This recent Nature paper reported that perfusing aged mouse brains with young cerebrospinal fluid (CSF) is effective to improve memory capacity. Noticeably, a surge of oligodendroglial proliferation and differentiation (oligodendrogenesis) is the most prominent phenomenon in the aged mouse hippocampus after treatment with the young CSF. Oligodendrogenesis has been shown to be required for multiple brain functions, such as learning new skills and remote memory consolidation, which is greatly diminished in aged brains.
In addition, the authors identified fibroblast growth factor 17 as the key player in boosting oligodendrogenesis in vivo and in vitro. Manipulations of this signal pathway were sufficient to duplicate the effects of CSF on oligodendrogenesis and memory capacity. In line with this notion, previous studies have shown that enhancing myelination, either by drugs or by cell-specific manipulation, is enough to boost the performance of aged mice in memory-related tasks.
Together, these results indicate that oligodendrogenesis plays a pivotal role in slowing down age-related functional decline, underlining flourishing oligodendrogenesis as a promising way to put a brake on brain aging.
View all comments by Feng MeiTrueBinding
This is an exciting paper by Tony Wyss-Coray's group, investigating the role of the transcription factor Serum Response Factor (SRF), and the growth factor Fgf17, in the CSF. Their ability to restore oligodendrocytes and improve cognition is fascinating. If I remember correctly, Wyss-Coray published a paper in 2014 in which he demonstrated that exposure to young blood counteracts aging at the molecular, structural, functional, and cognitive levels in the aged hippocampus. They identified CREB in young blood as one member of the regulatory network underlying structural and cognitive enhancements.
It will be interesting to investigate the mechanism of action SRF and Fgf17 and the role of these proteins in neurodegenerative diseases associated with traumatic brain injury or spinal cord injury.
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