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dc.contributor.authorOzen, Hasan
dc.description.abstractCerebellar cortical degeneration with primary Purkinje cell degeneration is common in dogs. However, primary granule cell degeneration without the Purkinje cell loss is extremely rare and has only been reported in a few cases. The purpose of this study was to characterize a spontaneously occurring inherited neurologic disorder in Jack Russell Terriers. In this disorder, there is extensive granule cell degeneration without Purkinje cell loss. I intended to determine the type of cell death and examine the underlying causes of this cell death in the ataxic Jack Russell Terriers. Apoptosis is known to play an important role during the normal development of cerebellum and in some neurodegenerative disorder. However, apoptosis has not been investigated in dogs with cerebellar cortical degeneration. Using in situ end labeling and electron microscopy in a group of ataxic and non-ataxic dogs, I identified the means of cell death in granule cells as apoptosis. Two of the important mediators of apoptosis, Bax and Bcl-2, were investigated immunohistochemically. Bax was found to be overexpressed in granule cells in the ataxic dogs. There was no difference in the expression of Bcl-2 between the ataxic and non-ataxic dogs. Immunohistochemical examination for neurotrophins, nerve growth factor (NGF) and neurotrophin (NT)-3, and the common neurotrophin receptor p75NTR showed that the number of granule cells with increased p75NTR-immunoreactivity in the internal granule cell layer increases in the ataxic dogs, while the number of nerve growth factor immunoreactive granule cells in the molecular layer decreases in these dogs. NT-3 expression does not show any difference between the ataxic and non-ataxic dogs. The overall results indicate that apoptosis is the mean of cell degeneration in the ataxic Jack Russell Terries, and this apoptosis is mediated by the action of pro-apoptotic molecule, Bax. A decrease in the NGF or overexpression of p75NTR, which is also known to mediate apoptotic cell death in certain occasions, might be responsible for the initiation of granule cell death in the Jack Russell Terriers.
dc.subjectCerebellar cortical degeneration
dc.subjectNerve Growth Factor
dc.titleNeurotrophin and apoptosis mediator expression in primary granule cell degeneration of Jack Russell Terrier
dc.description.majorVeterinary Pathology
dc.description.advisorK. Paige Carmichael
dc.description.committeeK. Paige Carmichael
dc.description.committeeJaroslava Halper
dc.description.committeeElizabeth W. Howerth
dc.description.committeeThomas F. Murray
dc.description.committeeJulie E. Coffield

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