Author
Listed:
- Tal Iram
(Stanford University School of Medicine
Stanford University School of Medicine)
- Fabian Kern
(Stanford University School of Medicine
Saarland University
Saarland University Campus)
- Achint Kaur
(Stanford University School of Medicine
Stanford University School of Medicine)
- Saket Myneni
(Stanford University School of Medicine
Stanford University School of Medicine)
- Allison R. Morningstar
(Stanford University School of Medicine
Stanford University School of Medicine)
- Heather Shin
(Stanford University School of Medicine
Stanford University School of Medicine)
- Miguel A. Garcia
(Stanford University School of Medicine)
- Lakshmi Yerra
(Palo Alto Veterans Institute for Research)
- Robert Palovics
(Stanford University School of Medicine
Stanford University School of Medicine)
- Andrew C. Yang
(Stanford University School of Medicine
Stanford University School of Medicine)
- Oliver Hahn
(Stanford University School of Medicine
Stanford University School of Medicine)
- Nannan Lu
(Stanford University School of Medicine
Stanford University School of Medicine)
- Steven R. Shuken
(Stanford University School of Medicine
Stanford University School of Medicine
Stanford University)
- Michael S. Haney
(Stanford University School of Medicine
Stanford University School of Medicine)
- Benoit Lehallier
(Stanford University School of Medicine
Stanford University School of Medicine)
- Manasi Iyer
(Stanford University School of Medicine)
- Jian Luo
(Stanford University School of Medicine
Palo Alto Veterans Institute for Research)
- Henrik Zetterberg
(Sahlgrenska Academy at the University of Gothenburg
Sahlgrenska University Hospital
UCL Institute of Neurology, Queen Square
UK Dementia Research Institute at UCL)
- Andreas Keller
(Stanford University School of Medicine
Saarland University
Saarland University Campus
Center for Bioinformatics, Saarland Informatics Campus)
- J. Bradley Zuchero
(Stanford University School of Medicine)
- Tony Wyss-Coray
(Stanford University School of Medicine
Stanford University School of Medicine
Stanford University School of Medicine)
Abstract
Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies to slow brain ageing1–3. 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.
Suggested Citation
Tal Iram & Fabian Kern & Achint Kaur & Saket Myneni & Allison R. Morningstar & Heather Shin & Miguel A. Garcia & Lakshmi Yerra & Robert Palovics & Andrew C. Yang & Oliver Hahn & Nannan Lu & Steven R. , 2022.
"Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17,"
Nature, Nature, vol. 605(7910), pages 509-515, May.
Handle:
RePEc:nat:nature:v:605:y:2022:i:7910:d:10.1038_s41586-022-04722-0
DOI: 10.1038/s41586-022-04722-0
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