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Investigation of Molecular and Cellular Mechanism 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.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/42811
Date22 November 2013
CreatorsDedeagac, Asli
ContributorsKaplan, David R.
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

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