Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17
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.
https://www.nature.com/articles/s41586-022-04722-0
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.
https://www.nature.com/articles/s41586-022-04722-0
Nature
Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17
Nature - Fgf17 in young CSF boosts oligodendrocyte progenitor cell proliferation and differentiation in the aged hippocampus, improving memory function.
Forwarded from partially unsupervised
Ирония высшего порядка: Гугл отчаялся приучить т.н. датасайнтистов нормально структурировать код или хотя бы линейно исполнять ячейки в Jupyter ноутбуках, и потому запустил kaggle-соревнование, в котором нужно предиктить порядок исполнения этих самых ячеек.
Forwarded from Axis of Ordinary
"Is AI task performance a type of submartingale, like a stock market index that goes up over time, but where each particular movement is intrinsically unpredictable?" https://www.lesswrong.com/posts/G993PFTwqqdQv4eTg/is-ai-progress-impossible-to-predict
Forwarded from Axis of Ordinary
"After showing a few examples, large language models can translate natural language mathematical statements into formal specifications."
[...]
"It handles the negation “there is no function” by proof-by-contradiction. It understands the phrase “into itself” and correctly formalizes the co-domain of f."
[...]
"Our finding hence shows a very surprising capability of these models. They learned very general and transferable knowledge that allows them to work with low-resource formal language."
Thread: https://threadreaderapp.com/thread/1529886847953870848.html
[...]
"It handles the negation “there is no function” by proof-by-contradiction. It understands the phrase “into itself” and correctly formalizes the co-domain of f."
[...]
"Our finding hence shows a very surprising capability of these models. They learned very general and transferable knowledge that allows them to work with low-resource formal language."
Thread: https://threadreaderapp.com/thread/1529886847953870848.html