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The Role of Bone Morphogenetic Proteins in Reactive Gliosis after Demyelinating Spinal Cord Lesions

Fuller, Molly Lynn
http://rave.ohiolink.edu/etdc/view?acc_num=case1183990990

Abstract Details

2007, Doctor of Philosophy, Case Western Reserve University, Neurosciences.
The response of glial cells to injury of the adult central nervous system (CNS) leads to formation of a glial scar, a dense network of astrocytes and extracellular matrix molecules. While the scar plays a protective role by creating a barrier between the CNS parenchyma and external environment, it is also one of the major factors leading to incomplete repair of tissue architecture and function. In this thesis, I examine the importance of bone morphogenetic proteins in glial cell reactivity after demyelinating injury. Using the model system of the dorsal columns of the rat thoracic spinal cord, I examined the acute behaviors of astrocytes and NG2+ glial precursors after LPC-induced demyelinating lesions. At three days after injection, levels of BMP4 and BMP7 are increased in the lesion, and the majority of cells contained phosphorylated Smad 1/5/8 in their nuclei. Expression of glial fibrillary acidic protein (GFAP) is increased in astrocytes at the lesion edge and expression of NG2 is increased on cells filling the core of the lesion. Vimentin is up-regulated in both of these populations. Cultures of mature astrocytes or NG2+ glial cells were treated with BMP4 or BMP7 and the quantity of chondroitin sulphate proteoglycans (CSPGs) were found to be increased at both the protein and RNA levels. Astrocytes doubled the mRNA levels for CSPG core proteins aggrecan and neurocan after one day of BMP treatment and displayed a maximum of 4-fold increase in CSPG protein after 4 days of treatment. NG2+ cells increased their aggrecan mRNA levels 14-fold and neurocan and versican levels 2-fold after 3 days of BMP4 treatment. BMP7 caused similar but smaller changes. These data link BMP signaling to glial scar formation after demyelination. The increase of CSPGs by BMPs is an event that is likely to inhibit migration of oligodendrocyte precursors and extension of regenerating neurites through the area of damage. Additionally, remyelination requires the recruitment of glial precursors and differentiation of those precursors into oligodendrocytes capable of myelination. Evidence of active BMP signaling in these cells, as shown here, would likely lead to the differentiation of precursors into astrocytes rather than oligodendrocytes. This work reveals BMPs as a possible therapeutic target for limiting glial scarring and optimizing the area of damage for remyelination.
Robert Miller (Advisor)
150 p.
Biology, Neuroscience
BMP; CSPG; glial scar; demyelination; CNS

Recommended Citations

Citations

  • Fuller, M. L. (2007). The Role of Bone Morphogenetic Proteins in Reactive Gliosis after Demyelinating Spinal Cord Lesions [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1183990990

    APA Style (7th edition)

  • Fuller, Molly. The Role of Bone Morphogenetic Proteins in Reactive Gliosis after Demyelinating Spinal Cord Lesions. 2007. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1183990990.

    MLA Style (8th edition)

  • Fuller, Molly. "The Role of Bone Morphogenetic Proteins in Reactive Gliosis after Demyelinating Spinal Cord Lesions." Doctoral dissertation, Case Western Reserve University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1183990990

    Chicago Manual of Style (17th edition)

case1183990990
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© 2007, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.