Our lab studies factors that control the maturation of oligodendrocytes, the myelinating cells of the central nervous system, from stem cells through to myelination.
Key words: oligodendrocytes, myelin, growth factors, programmed cell death, oxidative stress.
Description of Research
In the central nervous system, oligodendrocytes synthesize myelin as an extension of their plasma membranes. This myelin wraps axons and allows rapid and efficient conduction of nervous impulses. Destruction of myelin through injury, such as birth injury leading to cerebral palsy, or disease, such as multiple sclerosis, causes extreme loss of function. Oligodendrocyte precursors and stem cells remain in the CNS following the pathology and are potentially capable of forming mature oligodendrocytes and then myelin. However, their maturation is severely limited. Possible reasons for this include the inhibitors present in the area that impede maturation and astrogliosis in which astrocytes form physical and chemical barriers to regeneration. Our goal is to identify factors in the CNS that promote or inhibit the development of mature oligodendrocytes both during development and disease. On going areas of investigation in the lab include: The role and interactions of dorsal signaling factors, bone morphogenetic proteins (BMPs) and Wnts, in the development of oligodendrocytes and myelination. -The fate of oligodendrocyte maturation and myelination following hypoxic/ischemic injury in the central nervous system. The role of BMPs in oxidative stress following birth injury or demyelination in the adult. Rotation projects for 2012-2013: 1) The role of BMP in a model of dysmyelinating disease. 2) The role of intermediates such as NF-kB and Nrf-2 in oxidative stress during oligodendrocyte maturation. 3)The role of dorsal signaling factors and reactive oxygen species in oligodendrocyte:neuronal co-cultures. 3)The effect of antri-retroviral therapy on oligodendrocyte maturation.
Kristin Carmines research assistant
Brigid Jensen graduate student
Hubert Monnerie research associate
- Research Assistant Professor of Neurology at University of Pennsylvania School of Medicine (1989 – 1995)
- Research Associate Professor of Neurology at University of Pennsylvania School of Medicine (1995– present)
- Ph.D., Biology, University of Pennsylvania (1984)
- M.S., Pathology, Hahnemann University (1977)
- A.B., Biology, Vassar College (1974)
- Reid, M.V., Murray, K. A., Marsh, E.D., Golden, J. A., Simmons, R.A., Grinspan, J. B.. Delayed myelination in an intrauterine growth retardation model is mediated by oxidative stress upregulating BMP4. Journal of Neuropathology Experimental Neurology. Vol 71(7) . 2012:640-653.
- Feigenson, K., Reid, M., See, J., Crenshaw, E.B. III, Grinspan, J. B.. Canonical Wnt signaling requires the BMP pathway to inhibit oligodendrocyte maturation. ASN NEURO. Vol 3. 2011:147-158.
- French, H. M., Reid, M., Mamontov, P., Simmons, R. A., Grinspan, J. B.. Oxidative stress disrupts oligodendrocyte maturation. Journal of Neuroscience Research. Vol 87. 2009:3076-3087.
- Feigenson, K., Reid, M., See, J., Crenshaw E.B. III, Grinspan, J. B.. Wnt signaling is sufficient to perturb oligodendrocyte maturation. Molecular and Cellular Neuroscience. Vol 42. 2009:255-265.
- See, J. and Grinspan, J. B.. Sending mixed signals: bone morphogenetic proteins in myelination and demyelination. Journal of Neuropathology Experimental Neurology. Vol 68. 2009:595-604.
- Ara, J., See, J., Mamontov, P., Hahn, A., Bannerman, P. Pleasure, D., Grinspan, J.B.. Bone morphogenetic proteins 4, 6, and7 are upregulated in mouse spinal cord during experimental autoimmune encephalomyelitis. Journal of Neuroscience Research. Vol 86. 2008:125-135.
- Marek, R., Caruso, M. ,Rostami, A.M., Grinspan, J.B., Das Sarma, J.. CD11b magnetic cell sorting: a fast and effective method of concurrent isolation of high purity viable astrocytes and microglia from neonatal mouse brain tissue.. J Neuroscience Methods. Vol 175. 2008:108-118.
- See, J., Mamontov, P., Ahn K., Wine-Lee, L., Crenshaw III, E.B., Grinspan, J. B.. BMP mutant mice exhibit glial cell maturation defects. Molecular and Cellular Neuroscience. Vol 35. 2007:171-182.
- Huang, Y., Grinspan, J.B, , Abrams, C. K., Scherer, S. S.. Pannexin 1 is expressed by neurons and glia but does not form functional gap junctions. Glia. Vol 55. 2007:46-56.
- See, J., Zhang, X., Eraydin, N. Mun, S.B., Mamontov, P., Golden, J. Grinspan, J.B.. Oligodendrocyte maturation is inhibited by bone morphogenetic protein. Molecular and Cellular Neuroscience. Vol 26. 2004:481-492.