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Chemical and Metabolomic Analyses of Cuprizone-Induced Demyelination and Remyelination

Taraboletti, Alexandra Anna
http://rave.ohiolink.edu/etdc/view?acc_num=akron1498535047689141

Abstract Details

2017, Doctor of Philosophy, University of Akron, Chemistry.
The cuprizone intoxication model of demyelination and remyelination has long been used to test myelin regenerative therapies for neurodegenerative diseases such as multiple sclerosis. Mice develop reversible and region-specific oligodendrocytosis and demyelination when fed this small molecule copper chelator. While the histopathology of the model has been well documented, to date, there is no consensus on cuprizone’s cellular mechanism of action, and whether it involves the chelation of copper in vivo. Additionally, a variant model has been employed that combines rapamycin with cuprizone, causing more robust demyelination. In this model, rapamycin is hypothesized to suspend oligodendrocyte differentiation via the disruption of mTOR. In this work, the spatial and temporal effects of cuprizone were extensively studied in the in vivo model, and compared to a newly developed in vitro model. Global metabolomic and lipidomic profiling were utilized as analytic tools to determine biochemical pathways altered by cuprizone, rapamycin, or cuprizone and rapamycin treatments. Furthermore, oligodendrocyte differentiation in relation to mTOR was explored with transcriptomics. Together this work utilizes OMICS technology paired with analytical techniques to investigate both the chemical nature of cuprizone and the biological function of the oligodendrocyte, gaining insight into the molecular interplay that occurs during the processes of demyelination and remyelination.
Leah Shriver, Dr. (Advisor)
Richard Londraville , Dr. (Committee Member)
Sailaja Paruchuri , Dr. (Committee Member)
Chrys Wesdemiotis, Dr. (Committee Member)
Christopher Ziegler, Dr. (Committee Member)
207 p.
Biochemistry; Bioinformatics; Cellular Biology; Chemistry
metabolomics; cuprizone; multiple sclerosis; copper; transcriptomics; neurodegenerative; oligodendrocytes; myelin; rapamycin; mTOR; BCAA; TDO; demyelination; remyelination;

Recommended Citations

Citations

  • Taraboletti, A. A. (2017). Chemical and Metabolomic Analyses of Cuprizone-Induced Demyelination and Remyelination [Doctoral dissertation, University of Akron]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=akron1498535047689141

    APA Style (7th edition)

  • Taraboletti, Alexandra. Chemical and Metabolomic Analyses of Cuprizone-Induced Demyelination and Remyelination. 2017. University of Akron, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=akron1498535047689141.

    MLA Style (8th edition)

  • Taraboletti, Alexandra. "Chemical and Metabolomic Analyses of Cuprizone-Induced Demyelination and Remyelination." Doctoral dissertation, University of Akron, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=akron1498535047689141

    Chicago Manual of Style (17th edition)

akron1498535047689141
2,986
© 2017, some rights reserved.Creative Commons License Chemical and Metabolomic Analyses of Cuprizone-Induced Demyelination and Remyelination by Alexandra Anna Taraboletti is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Akron and OhioLINK.