Myelin repair in the central nervous system has been demonstrated in both experimental models and human studies as a normal physiological response to myelin injury. However, in chronic inflammatory demyelinating disorders of the CNS, such as multiple sclerosis (MS), myelin repair is usually incomplete. Previous work in our lab has shown that remyelination can be increased four fold by in vivo administration of monoclonal antibodies directed against undetermined CNS antigens. This remyelination promotion is seen in both immune-mediated and toxic-traumatic models of MS. One possible mechanism by which the antibodies may mediate remyelination is through binding to a unique receptor on oligodendrocytes or glial progenitor cells. This receptor binding may mimic normal signals that induce or coordinate myelination. Many signal transduction cascades involve intracellular calcium changes. In order to investigate the possibility that remyelination promoting antibodies directly activate glial cells, we will use ratiometric fluorescent monitoring of intracellular calcium concentrations ([Ca2+]i). The proposed research will characterize the potential of remyelination promoting antibodies to physiologically activate CNS cells, determine the cell phenotypes involved and the contribution of differentiation state.
Specific aim two will utilize phamacological and biochemical techniques to begin to elucidate the intracellular signal transduction components stimulated by the remyelination promoting antibodies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS011006-03
Application #
6393272
Study Section
Special Emphasis Panel (ZRG1-ALTX-4 (03))
Program Officer
Kerza-Kwiatecki, a P
Project Start
2001-09-30
Project End
2002-02-15
Budget Start
2001-09-30
Budget End
2002-02-15
Support Year
3
Fiscal Year
2001
Total Cost
$20,734
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905