A component of the myelin sheath surrounding spinal cord axons regulates the growth of neighboring unmyelinated neurons by sequestering NGF, von Büdingen et al. reveal.
Oligodendrocytes form an insulating myelin sheath around the axons of central nervous system neurons. This sheath is lost in multiple sclerosis and other demyelinating diseases, but it’s unclear why this often results in chronic pain, since most pain-sensing (nociceptive) neurons are not myelinated to begin with. Von Büdingen et al. found that the myelin sheath can bind and sequester NGF, a growth factor that promotes the growth and survival of nociceptive neurons.
Specifically, NGF bound with high affinity to myelin oligodendrocyte glycoprotein (MOG), a protein expressed on the outer surface of the myelin sheath. Mice lacking MOG displayed an increased sprouting of nociceptive fibers in their spinal cords, suggesting that MOG might usually limit the growth of these neurons by lowering the local concentration of free NGF.
Other neurotrophic factors, like BDNF and NT-3, can be sequestered by truncated versions of their receptors. Although MOG is unrelated to the NGF receptor TrkA, its extracellular region folds into a similar Ig-like domain. MOG’s ability to limit nociceptive fiber sprouting and pain sensation is likely to be lost in multiple sclerosis patients. MOG’s function may also be important following peripheral nerve injury, when increased levels of NGF are produced within the central nervous system. The authors now want to test these ideas by developing better mouse models of neuropathic pain and examining these in the context of demyelination.
Text by Ben Short