The basic objective of the proposed research is characterization of factors that may contribute to remyelination in M.S. The novel aspect of the proposal is that we will emphasize the potential role of platelets in remyelination associated with multiple sclerosis. Other investigators have suggested that T cells and other components of the """"""""standard"""""""" immune system promote remyelination and neuroprotection through neurotrophins. We will not ignore this possibility in our research. However, initially, the proposed research will emphasize the possible role of platelets in remyelination. The role of platelets in remyelination is an area of research that has not been a topic for investigation in the past. For this reason the current proposal is submitted as a developmental grant. In multiple sclerosis, it is well established that in some lesions there is remyelination that is likely to be responsible for some of the recovery that can occur after some multiple sclerosis attacks. In the long term, areas that have been severely demyelinated probably do not permit a return of function unless remyelination occurs. A major impetus for this project includes recent publications that have emphasized the presence of oligodendrocytes in some areas that remain demyelinated. Also, many of the oligodendrocytes express receptors for known growth factors. Platelets are known to release the neurotrophins that bind these receptors. These growth factors promote the proliferation and differentiation of oligodendrocytes into mature cells. Other investigations in vitro and in vivo with human material has suggested that T cells may be an important source of neurotrophins, especially BDNF. By contrast, our preliminary data investigating BDNF indicates that platelets are a major source of BDNF.
The specific aims of this proposal will include extending our preliminary studies, reviewed below, to include additional control subjects as well. We will further characterize production of additional neurotrophins by other components of the peripheral blood mononuclear cells with initial emphasis on platelets. In addition we will extend our preliminary study examining the presence of platelets in multiple sclerosis lesions. We plan to examine active and chronic lesions including the simultaneous localization of specific neurotrophins with various PBMC cell types and platelets.
