Brain, Vol. 125, No. 1, 75-85,
January 1, 2002
© 2002 Oxford University Press
BDNF and gp145trkB in multiple sclerosis brain lesions: neuroprotective interactions between immune and neuronal cells?
,2,31Institute for Neuropathology, Charité, Humboldt-University, Berlin, 2Institute for Clinical Neuroimmunology, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, 3Department of Neuroimmunology, Max-Planck-Institute for Neurobiology, Martinsried, Germany and 4Department of Neuroimmunology, Brain Research Institute, University of Vienna, Austria Correspondence to: Professor Dr Hans Lassmann, Brain Research Institute, Department of Neuroimmunology, Spitalgasse 4, A-1090 Vienna, Austria E-mail: hans.lassmann{at}univie.ac.at
*These authors contributed equally to this paper Present address: Brain Research Institute, University of Zurich, CH-8057 Zurich, Switzerland
Recent immunohistological and imaging studies emphasize the crucial role of axonal injury in determining the extent of permanent neurological deficits in patients with multiple sclerosis. We have recently shown that human immune cells are capable of producing the neurotrophin brain-derived neurotrophic factor (BDNF), which can prevent axonal and neuronal damage after various pathological insults. BDNF imported into the CNS by immune cells would thus be an attractive candidate for mediating neuroprotective effects in multiple sclerosis. The aim of the present study was to perform a detailed immunohistochemical analysis of the expression of BDNF and its receptor truncated trkB tyrosine kinase receptor (gp145trkB) in a series of multiple sclerosis brain lesions. Our data show that various types of neurones throughout the brain are BDNF immunopositive in multiple sclerosis patients as well as in controls. Furthermore, in multiple sclerosis lesions, BDNF is primarily present in immune cells (T cells, macrophages/microglia) and reactive astrocytes. The number of BDNF immunopositive cells correlates with lesional demyelinating activity. The BDNF receptor gp145trkB is found in neurones in the immediate vicinity of multiple sclerosis plaques as well as in reactive astrocytes within the lesion, but not in immune cells. Our results demonstrate that both BDNF and gp145trkB are expressed in multiple sclerosis lesions. This suggests that BDNF and gp145trkB are involved in immune-mediated neuroprotective interactions in multiple sclerosis, and supports the concept that immune cells produce both damaging and protective factors in multiple sclerosis lesions.
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