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 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.
Recommended Citation
Kuypers, Nicholas John, "Functional implications of demyelination and the molecular control of remyelination in the adult mouse." (2014). Electronic Theses and Dissertations. Paper 786.
https://doi.org/10.18297/etd/786
