I Want To...
I Want To...
Find Research Faculty
Enter the last name, specialty or keyword for your search below.
School of Medicine
I Want to...
Why does the peripheral nervous system regenerate, but not the CNS?
SCHNAAR: When nerve damage occurs, debris in the area carries signals that tell axons not to grow. Cells like macrophages are meant to clean up this debris, and the PNS— neatly laid out like railroad tracks—is fairly accessible to them. Then axons can regrow on those “tracks.” The CNS, however, is like a ton of spaghetti in a trash compactor; macrophages can’t get access.
From a broader perspective, why evolve a nervous system that can’t self-repair?
SCHNAAR: The CNS has maximized storage capacity per unit space. While this has increased our information processing by an order of magnitude, we had to give up the flexibility of repair to prevent misconnections.
Given that the system is set up to prevent inappropriate connections, how do you know that altering it with sialidase (above) won’t increase wrong circuits?
SCHNAAR: We can’t know for sure, but there is precedence for axons’ being able to find their way intrinsically. Also, the nervous system seems able to deal with imperfect circuitry. When the wrong nerve is connected surgically, the brain, over time, can sort things out and restore function.
Circuits may be OK, but is there a risk that using sialidase will destabilize existing axons and kill them?
SCHNAAR: I don’t believe so. Axons in mice without proper gangliosides don’t begin to degenerate until the mice are 3 to 6 months of age. That tells us to block inhibitors of axon regeneration only long enough to let axons start regrowth. Then we withdraw sialidase and allow axon surfaces to repopulate with gangliosides. Appropriate interaction with myelin-associated glycoprotein returns and with it, long-term stabilization.
Your lab has shown that MAG is critical for inhibiting regeneration, but also that it stabilizes myelin, thus inhibiting degeneration. This seems like a contradiction of sorts.
SCHNAAR: Stability cuts two ways. Myelin is laid down late in development, after most of the axonal network forms. It contains stabilizing signals that both nurture axons and halt their outgrowth—important in the crowded CNS to avoid inappropriate sprouting and connections. In CNS injury, however, these same stabilizing signals sit there and impede the new sprouting required for repair.