Cerebrospinal fluid (CSF) from young mice improved the ability of older mice to recall recent memories, according to an NIA-funded study published in Nature. The findings suggest that at least one CSF protein may trigger the growth and maturation of cells that help protect brain function in older mice. The study results appear to underscore the therapeutic potential of CSF proteins found in young mice fluid as well as the role that these “helper cells” play in brain aging.
CSF is a clear fluid that surrounds the brain and spinal cord, providing protection as well as vital nutrients, including proteins, fats, sugars, and vitamins. The composition of CSF changes with age, and it is not clear whether these changes contribute to age-related memory loss.
Previously, scientists discovered that blood from young mice may rejuvenate the brains of older mice. In this more recent study, an international team of scientists from Stanford University; Palo Alto Veterans Institute for Research; Saarland University, Germany; University of Gothenburg, Sweden; and University College London Queen Square Institute of Neurology explored whether CSF from young mice might have similar effects.
To address this possibility, the researchers first tested whether CSF from young mice influenced the ability of older mice to recall memories of foot shocks. Mice are considered adults at two months old and have a life expectancy of approximately two years. First, a group of 20-month-old mice was trained with foot shocks to freeze in motion when presented with a light and sound cue. Then CSF, drawn from three-month-old mice, was injected into the brains of some of the older mice. The mice that received the CSF froze in motion more often when presented with the cue than those that received a control fluid, suggesting the young CSF helped the older mice remember better.
Next, the researchers searched for clues to how this happened by examining the brains of the older mice. Their results suggest that the young CSF caused stem cells, called oligodendrocyte progenitor cells (OPCs), to multiply and mature. Mature oligodendrocytes help neurons by creating myelin, which is a waxy material that insulates long, stringy axons, a part of neurons that relays signals to other cells. Much of this was observed in the hippocampus, a region of the brain involved in memory. Other studies of mice have also found links between brain myelin and memory.
Further experiments revealed that a protein called Fgf17 may have played a critical role in improving memory and triggering OPC growth. Mice injected with Fgf17 performed better on the foot shock memory tests and had greater OPC growth and maturation than those that received a control solution. In contrast, mice treated with a blocker of Fgf17 activity performed worse on the memory tests than those receiving a control drug. Moreover, the Fgf17 blocker inhibited the OPC growth in the presence of young CSF.
The results support the idea that the CSF and myelinating helper cells may play a critical role in the aging brain. Furthermore, by studying Fgf17 and other factors found in younger CSF, scientists may discover new clues to treating age-related brain disorders.
This research was supported in part by NIA grants RF1-AG064897-02 and T32AG000266.
Reference: Iram T, et al. Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17. Nature. 2022;605(7910):509-515. doi: 10.1038/s41586-022-04722-0.