published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

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Axon degeneration is a selective elimination of axons, which plays a crucial role during development, injury, and maintenance of neuronal connections. The p75 neurotrophin receptor (NTR) is responsible for maintaining the specificity of neuronal connectivity in parts of the adult brain by inducing the degeneration of aberrantly growing axons into myelinated tracts. The objective of this study is to identify and characterize the signaling pathways used by p75NTR to mediate axon degeneration on myelin. Since p75NTR signals via JNK/Bax/caspase pathway to cause apoptosis, I asked whether this pathway might also be involved in axon degeneration. I observed that inhibition of JNK or Bax significantly decreased myelin-induced axonal degeneration, while depolarization of axons with potassium chloride prevented axonal degeneration on myelin. Together, these results suggest that p75NTR-dependent, myelin-mediated axon degeneration occurs via JNK/BAX signaling, and that neural activity is important for the prevention of myelin-induced axonal degeneration.

Axon degeneration is a selective elimination of axons, which plays a crucial role during development, injury, and maintenance of neuronal connections. The p75 neurotrophin receptor (NTR) is responsible for maintaining the specificity of neuronal connectivity in parts of the adult brain by inducing the degeneration of aberrantly growing axons into myelinated tracts. The objective of this study is to identify and characterize the signaling pathways used by p75NTR to mediate axon degeneration on myelin. Since p75NTR signals via JNK/Bax/caspase pathway to cause apoptosis, I asked whether this pathway might also be involved in axon degeneration. I observed that inhibition of JNK or Bax significantly decreased myelin-induced axonal degeneration, while depolarization of axons with potassium chloride prevented axonal degeneration on myelin. Together, these results suggest that p75NTR-dependent, myelin-mediated axon degeneration occurs via JNK/BAX signaling, and that neural activity is important for the prevention of myelin-induced axonal degeneration.

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Thesis (Ph. D.)--Wake Forest University. Dept. of Physics, 2003. / Vita. Includes bibliographical references (leaves 108-114).

Thesis (Ph. D.)--University of Hong Kong, 1991.

Honors Project--Smith College, Northampton, Mass., 2010. / Includes bibliographical references (p. 91-96).

Thesis (Ph. D.)--Illinois State University, 2005. / Title from title page screen, viewed September 26, 2006. Dissertation Committee: Anthony J. Otsuka (chair), Radheshyam Jayaswal, Kevin A. Edwards, David L. Williams, Hou Tak Cheung. Includes bibliographical references (leaves 110-124) and abstract. Also available in print.