CALCIUM-MEDIATED DEGENERATION OF THE AXONAL CYTOSKELETON IN THE OLA MOUSE

The C57BL/Ola (Ola) mouse is a mutant substrain in which transected ax ons undergo very slow Wallerian degeneration. Because axonal degradati on during Wallerian degeneration is calcium dependent, we tested wheth er Ola axons are susceptible to calcium-mediated axonal degeneration b y comparing neurofilament degradation between Ola and C57BL/6 mice in sciatic nerve explants. Using immunoblot analysis of neurofilament deg radation and electron microscopy we found that as in normal axons, axo nal degeneration in the Ola is calcium dependent. However, when compar ed with normal animals, higher levels of calcium were required for com plete degradation of neurofilaments in Ola nerve, suggesting a relativ e insensitivity to calcium-mediated degeneration in the Ola. We conclu de that calcium-activated proteases are present and active in Ola axon s but that higher levels of calcium are required to accomplish complet e axonal degradation. These results suggest a possible mechanism for p rolonged survival of transected Ola axons and provide potential insigh t into the pathophysiology of axonal degeneration in injury and diseas e.