Nature: Cerebrospinal fluid from young mice/humans restores oligodendrocyte proliferation and memory in aged mice

Recent studies have shown that systemic interventions in organisms have shown great promise in reversing aging-related aspects of brain tissue, such as the transfer of young plasma into the blood of the elderly to rejuvenate the aging brain and restore memory function

Professor Tony.

Young mouse/human CSF

Regulation of oligodendrocyte proliferation

The team first performed paired training of foot electrical stimulation and light/sound on 20-month-old old mice, and then divided the mice into two groups, which were injected with artificial cerebrospinal fluid (aCSF) and CSF from young mice (YM- CSF) for one week, and then perform memory test 3 weeks after training, and found that the mice in the YM-CSF injection group had better memory ability (Fig.

RNA-sequencing of the mouse hippocampus revealed that oligodendrocyte-related gene expression was greatly up-regulated, as was the expression of transcription factors that promote oligodendrocyte proliferation and differentiation (Fig.

In another group of mice injected with young human CSF (YH-CSF) and aged human CSF (AH-CSF), respectively, significantly increased OPC proliferation and differentiation were also found in YH-CSF-injected mice (Fig.

Figure 1.

Serum Response Factor (SRF) Mediated

Effects of young mouse/human CSF on OPCs

The team then used S4 U alkylated RNA metabolic sequencing technology to detect OPCs exposed to YH-CSF and found that 1 hour after exposure, SRF (inducing cell motility, proliferation and differentiation by regulating immediate early genes and actin cytoskeleton) The gene and its nascent mRNA expression were highest, the latter returning to baseline after 6 h, while the SRF-targeted genes reached the highest after 6 h exposure (Fig.

In addition, the actin cytoskeleton expression of OPCs after 6 h exposure to YH-CSF was also increased (Fig.

Figure 2.

It was also found that the number of SRF-positive OPCs was significantly reduced in the hippocampal CA1 region of aged mice (Fig.

However, after the injection of young CSF, the expression of SRF-targeted genes increased and was associated with pathways such as GTPase activity regulation and transcription factor binding (Fig.

Figure 3.

Fgf17 can simulate CSF

Effects on OPCs and memory

The team then screened SRF-targeted and activated genes in HENK293 cells using the SRE-GFP reporter system and found that fibroblast growth factor (Fgf) 17 and Fgf8 had the strongest and dose-dependent effects (Fig.

Then, Fgf17 was added to primary OPCs in vitro, and it was found to promote OPC proliferation and differentiation (Fig.

After that, injected Fgf17 antibody in young mice, it was found that the hippocampus-dependent behavioral function of the mice was decreased (Y maze, fear conditioning experiment), and neuroplasticity was reduced (Fig.

Figure 4.

in conclusion

CSF in young humans/mice can reverse decreased cognitive function, an ability presumably through Fgf17 in OPCs
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This research sheds new light on reversing aging
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references

Tal I, et al.
Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17.
Nature, 2022.
DOI: 10.
1038/s41586-022-04722-0.

Compilation author: KK (brainnews creative team)

Reviewer: Simon (Brainnews editorial department)

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