Our research aims are to obtain a better understanding of cellular/molecular events involved in glial cell development and myelin formation in the central and peripheral nervous systems (CNS and PNS) and to understand how myelin, myelin-forming cells, and axons are destroyed in autoimmune and inherited diseases of myelin.
New data about the normal functioning of myelin-forming cells and myelin-axon interactions will help us understand the pathogenic mechanisms involved in permanent neurological disability in human diseases of myelin.
Cellular/Molecular Biology of Myelination: Our aim is to obtain a better understanding of cellular/molecular events that regulate production and differentiation of oligodendrocytes and CNS myelination. Using transgenic mice, we study the role of myelin and myelin proteins in maintaining axonal function and survival. We also investigate the role of CNS progenitor cells as a source of new oligodendrocytes in the adult brain.
Pathogenesis of Neurological Disability in Multiple Sclerosis (MS): In these studies, we seek to determine the causes of MS, an inflammatory demyelinating disease of the CNS, and to therapeutically prevent irreversible neurological disability in MS patients. Historically, it has been assumed that axons were spared most of the pathological consequences of inflammatory demyelination. We have described axonal degeneration during demyelination and as a result of chronic demyelination. We also focus on neuronal degeneration and axonal pathology in the cerebral cortex and hippocampus of MS patients. Recent studies also focus on the therapeutic potential of progenitor cells to repair demyelinated or dysmyelinated brain.
Chen, Z., Jalabi, W., Shpargel, K.B., Farabaugh, K.T., Dutta, R., Yin, X., Kidd, G.J., Bergmann, C.C., Stohlman, S.A., and Trapp, B.D. Lipopolysaccharide-induced microglial activation and neuroprotection against experimental brain injury is independent of hematogenous TLR4. J Neurosci 32: 11706-15, 2012.
Dutta, R., Chang, A., Doud, M.K., Kidd, G.J., Ribaudo, M.V., Young, E.A., Fox, R.J., Staugaitis, S.M., and Trapp, B.D. Demyelination causes synaptic alterations in hippocampi from multiple sclerosis patients. Ann Neurol 69: 445-54, 2011.
Ohno, N., Kidd, G.J., Mahad, D., Kiryu-Seo, S., Avishai, A., Komuro, H., and Trapp, B.D. Myelination and axonal electrical activity modulate the distribution and motility of mitochondria at CNS nodes of ranvier. J Neurosci 31: 7249-58, 2011.
Lerner Research Institute
Mail Code NB21
9500 Euclid Avenue
Cleveland, Ohio 44195