Brain-derived neurotrophic factor BDNF is involved in MP4-induced experimental autoimmune encephalomyelitis (99.11)

Abstract

Abstract In multiple sclerosis and its animal model EAE, the role of BDNF is still not understood. Results have been ambiguous with some studies pointing to a neuroprotective role while others implied neurodestructive components. The use of gene-modified mice could largely help shed more light on the mechanisms BDNF plays in the disease. Thus far, however, such studies have not been done. Our results show significantly attenuated disease in terms of onset and severity in BDNF-deficient B6.129S4-BdnftmJae/J compared to wild-type mice. Strikingly, while wild-type mice displayed a classical TH1 cytokine profile in response to MP4, levels of antigen-specific T cells secreting IFN-γ and IL-2 were undetectable in the BDNF-deficient mice. In addition, lesion frequencies in the CNS were lower in these mice. Demyelination was also less severe. Analysis of the cellular composition of infiltrates revealed significantly higher numbers of B cells and CD8+ T cells in the wild-type mice. Our results suggest an important role for BDNF in the pathogenesis of MP4-induced EAE, which points to a more disease sustaining than neuroprotective function. Our initial immunological and histological studies suggest the involvement of this factor not only in mediating peripheral T cell responses, but also CNS pathology itself. Further studies are needed to dissect the mechanisms underlying our preliminary data.