Date on Master's Thesis/Doctoral Dissertation


Document Type

Doctoral Dissertation

Degree Name

Ph. D.


Anatomical Sciences and Neurobiology

Degree Program

Anatomical Sciences and Neurobiology, PhD

Committee Chair

Whittemore, Scott R.

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


Demyelination; Nervous system--Diseases


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.