Sequential loss of myelin proteins during Wallerian degeneration in the rat spinal cord

Abstract

Axotomy of nerve fibers leads to the subsequent degeneration of their distal part, a process termed Wallerian degeneration (WD). While WD in the peripheral nervous system is usually followed by regeneration of the lesioned axons, central nervous system (CNS) neurons are generally unable to regrow. In this study, we investigated the process of WD in the dorsal columns of the rat spinal cord rostral to a mid-thoracic lesion. We confirm earlier studies describing a very delayed microglial and an early and sustained astroglial reaction finally leading to scar formation. Interestingly, we found a differential time course in the loss of myelin proteins depending on their location. Proteins situated on the periaxonal myelin membrane such as myelin associated glycoprotein disappeared early, within a few days after lesion, concomitantly with cytoskeletal axonal proteins, whereas compact myelin and outer myelin membrane proteins such as MBP and Nogo-A remained for long intervals in the degenerating tracts. Two distinct mechanisms are probably responsible for this difference: processes of protein destruction emanating from and initially probably located in the axon act on a time scale of 1-3 days. In contrast, the bulk of myelin destruction is due to phagocytosis known to be slow, prolonged, and inefficient in the CNS. These results may also have implications for future intervention strategies aiming at enhancing CNS regeneration.