Inside your skull, your brain is floating in a clear liquid. This liquor cerebrospinalis, or cerebrospinal fluid (CSF), until recently was considered simply cushioning for the brain. It maintains a constant pressure in the skull, keeps the brain protected when it’s jolted, and carries waste away from the vital organ. Now, HHMI investigator Christopher A. Walsh has revealed that CSF does much more—it holds proteins that play irreplaceable roles in controlling brain development, growth, and health.
Walsh and his colleagues at Children’s Hospital Boston suspected that CSF has such important roles when they identified, in 2007, hundreds of proteins suspended in the fluid. In their latest work, they looked at how these proteins might affect the brain’s neural stem cells—the precursors to brain cells. They took bits of brain tissue from embryonic rats and bathed them in CSF from old and young rats. When exposed to the CSF from young animals, neural stem cells divided quickly. When soaked in older CSF, stem cells divided more slowly, and they more often differentiated into adult brain cells rather than renewing the population of stem cells.
“What we showed for the first time is that CSF’s role changes with time,” says Walsh.
The research team went on to determine that one particular CSF protein—called insulin-like growth factor 2 (Igf2)—largely controls neural stem cells. Knowing this, the scientists suspected that Igf2 could play a role in glioblastoma, a type of brain tumor in which neural stem cells are misdirected. So, in collaboration with another group, they analyzed a collection of CSF samples taken from glioblastoma patients. Indeed, they reported in Neuron on March 10, 2011, that more advanced cases of the cancer are associated with higher levels of Igf2 in the CSF. Whether this is a cause or an effect, they can’t yet conclude, but it ushers in a new mindset about CSF.
“This really changes how we think about a lot of things,” says Walsh. “The CSF clearly carries many different proteins that have active, and changing, roles in modulating the brain. There may be many other processes—potentially learning or behavioral states—that are modulated by CSF.”