Date on Master's Thesis/Doctoral Dissertation

5-2014

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Anatomical Sciences and Neurobiology

Degree Program

Anatomical Sciences and Neurobiology, PhD

Committee Chair

Whittemore, Scott R.

Committee Co-Chair (if applicable)

Magnuson, David S. K.

Committee Member

Magnuson, David S. K.

Committee Member

Hetman, Michal

Committee Member

Qiu, Meng Sheng

Committee Member

Li, Yong

Author's Keywords

MicroRNA; Cuprizone; Demyelination; Remyelination; Oligodendrocyte; Ethidium bromide

Subject

Demyelination; Nervous system--Diseases

Abstract

Oligodendrocyte (OL) loss contributes to the functional deficits underlying diseases with a demyelinating component (Gajjar et al., 1997; Miller et al., 2002). Remyelination can restore these deficits (Duncan et al., 2009). Chapter 1 is an introduction to de- and re-myelination thus providing the necessary background information for consideration in subsequent chapters. Ethidium bromide (EB) has been extensively used in the rat and cat as a model of spinal cord demyelination. However, this lesion has not been addressed in the adult mouse. Therefore, Chapters 2 and 3 characterize a model of chronic EB-induced spinal cord demyelination in the mouse which can be assessed behaviorally and electrophysiologically. MicroRNAs (miRNAs) possess both cell type- and differentiation stagespecific expression patterns (Lau et al., 2008). In oligodendrocytes (OLs), miRNAs regulate development and differentiation in vivo and in vitro, respectively (Lin et al., 2009; Zhao et al., 2010 and Dugas et al., 2010). However, it is unclear whether miRNAs involved in remyelination are distinct from those observed during normal myelination / development. Treatment of adult mice with the copper chelator cuprizone demyelinates specific brain regions which remyelinate following cuprizone cessation (Torkildsen et al., 2008). Therefore, Chapter 4 focuses on the role of oligodendroglial-specific miRNAs in cuprizone-induced de- and re-myelination. Lastly, Chapter 5 summarizes all of the data provided herein with an emphasis on clinical significance and therapeutic potential.

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