Grant: CIHR Fellowship

Peripheral nerves are wrapped by a lipid rich membrane, the myelin, which insulates the nerve fiber and is essential for rapid conductivity. In cases of injury, both the nerve and its myelin sheath degenerate. As myelin contains molecules that inhibit regeneration, it is important that myelin breaks down rapidly and be cleared by macrophages to allow for regeneration. Dr. Sam David´s laboratory has shown that lipolytic enzymes are important in triggering the breakdown and clearance of myelin after peripheral nerve injury. However, it is currently not known how the levels of these enzymes or their activation after nerve injury are increased. The aim of this proposal is to study the role of two types of molecules in this process. One class of molecules is cytokines that are released by the injured nerve. Another are molecules that form pore- like channels (Connexin 29 channels) that regulate the passage of ions, which could allow calcium to reach certain parts of the myelin sheath and trigger the activation of the lipolytic enzymes. Goals of this study are to characterize the expression and role of injury-induced cytokines in regulating the expression and activation of lipolytic enzymes and myelin breakdown after nerve injury; and also to assess the role of connexin 29 in this process. These studies could reveal new targets that can be studied to promote rapid myelin clearance after spinal cord injury to enhance regeneration, as myelin clearance is extremely slow in the spinal cord. They could also have important implications for clinical disorders of peripheral nerves such as peripheral neuropathies.