Huntington's Disease (HD) is a devastating neurodegenerative disorder caused by an expanded polyglutamine repeat within the Huntingtin gene IT15. In this study we demonstrated that Bcl-2 interacting mediator of cell death Extra Long (BimEL) protein expression was significantly increased in cells expressing mutant Huntingtin (mHtt). Moreover, striatal BimEL expression remained high in an R6/2 HD mouse model throughout the disease progression. Utilizing novel BimEL phospho-mutants we demonstrated the phosphorylation of Ser65 to be important for the stabilization of BimEL. We provided evidence that impaired proteasome function, increased JNK activity and reduced striatal BDNF lead to changes in the phosphorylation of BimEL, thereby promoting its stabilization specifically within the striatum of R6/2 mice. Furthermore, knocking down BimEL expression prevented mHtt-induced cell death in a HD cell culture. Taken together, these findings suggest that BimEL may contribute to the selective neurodegeneration and pathogenesis of HD. / by Rebecca Leon. / Thesis (Ph.D.)--Florida Atlantic University, 2012. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader.

Abstract not available

Thesis (M.Nurs. (Hons.)) -- University of Western Sydney, 2003. / Bibliography : leaves 240-253.

Thesis (Ph. D.)--University of California, San Diego, 1997. / Vita. Includes bibliographical references (leaves 174-188).

München, Techn. Univ., Diss., 2004.

Thesis (Ph. D.)--University of California, San Diego and San Diego State University, 2007. / Title from first page of PDF file (viewed June 11, 2007). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 171-178).

Amino acids and other ninhydrin-positive compounds were measured in post-mortem thalamus from 25 Huntington's choreics, 10 schizophrenics, 5 schizophrenic-like psychotics, and 23 controls dying without neurological disease. Gamma-aminobutyric acid (GABA) was significantly reduced in choreic thalami, in accord with deficiencies found in other brain regions choreics (Perry et al., 1973a,b). GABA was also significantly reduced in schizophrenic thalami, suggesting a biochemical link between these two diseases, and supporting the hypothesis of a defect in the GABA system in schizophrenia (Roberts, 1972). Homocarnosine, a GABA-containing dipeptide, was also low in choreic and 9 out of 10 schizophrenic thalami. One schizophrenic had extremely high homocarnosine. Glycerophosphoethanolamine was significantly elevated in Huntington's choreics, but not in schizophrenics. A number of other variables were considered for their potential influence on amino acid concentrations in thalamus. The majority of amino acids were found to rise in a significantly linear fashion in the interval 3 to 49 hours post-mortem, although other models might have described the change better. GABA, ornithine, histidine and tyrosine were found to decrease significantly with increasing age between 21 and 80 years, in controls. The effects of pre-mortem hypoxia, regional variation within the thalamus, and neuroleptic drug treatment could not be rigorously tested with these data. Neuroleptics were unlikely to have been the cause of group differences in GABA concentration, since they failed to deplete GABA in brain of chronically treated rats. On the other hand, bronchopneumonia and other causes of pre-mortem hypoxia could not be ruled out as potential contributers to reduced GABA in thalamus. / Medicine, Faculty of / Medical Genetics, Department of / Graduate

Adult neurogenesis is affected in neurodegenerative diseases and also represents an important therapeutic target. The goal of this dissertation research was to test the hypothesis that regeneration of neurons and glia in the adult brain can be manipulated by neurotrophic drugs in the context of two mouse models of neurodegenerative disease : Parkinson's disease and Huntington's disease.... These findings have implications for the pathophysiology of Huntington's disease and neurodegeneration in general. Specific alterations to the SVZ neurogenic niche parallel some of the pre-motor symptoms of Parkinson's disease and Huntington's disease. This dissertation research contributes to the growing body of literature concerning the pharmacological modulation of SVZ-derived neurogenesis designed to attenuate the progressive loss of neurons in neurodegenerative diseases and perhaps delay the onset of symptoms. / by Mark Harvey McCollum. / Vita. / Thesis (Ph.D.)--Florida Atlantic University, 2012. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader.

Paradoxically enhanced cognitive processes in neurological disorders provide vital clues to understanding neural function. However, what determines whether the neurological damage is impairing or enhancing is unclear. Here we use the performance of patients with two disorders of the striatum to dissociate mechanisms underlying cognitive enhancement and impairment resulting from damage to the same system. In a two-choice decision task, Huntington\'s disease patients were faster and less error prone than controls, yet a patient with the rare condition of benign hereditary chorea (BHC) was both slower and more error prone. EEG recordings confirmed significant differences in neural processing between the groups. Analysis of a computational model revealed that the common loss of connectivity between striatal neurons in BHC and Huntington\'s disease impairs response selection, but the increased sensitivity of NMDA receptors in Huntington\'s disease potentially enhances response selection. Crucially the model shows that there is a critical threshold for increased sensitivity: below that threshold, impaired response selection results. Our data and model thus predict that specific striatal malfunctions can contribute to either impaired or enhanced selection, and provide clues to solving the paradox of how Huntington\'s disease can lead to both impaired and enhanced cognitive processes.

Paradoxically enhanced cognitive processes in neurological disorders provide vital clues to understanding neural function. However, what determines whether the neurological damage is impairing or enhancing is unclear. Here we use the performance of patients with two disorders of the striatum to dissociate mechanisms underlying cognitive enhancement and impairment resulting from damage to the same system. In a two-choice decision task, Huntington\'s disease patients were faster and less error prone than controls, yet a patient with the rare condition of benign hereditary chorea (BHC) was both slower and more error prone. EEG recordings confirmed significant differences in neural processing between the groups. Analysis of a computational model revealed that the common loss of connectivity between striatal neurons in BHC and Huntington\'s disease impairs response selection, but the increased sensitivity of NMDA receptors in Huntington\'s disease potentially enhances response selection. Crucially the model shows that there is a critical threshold for increased sensitivity: below that threshold, impaired response selection results. Our data and model thus predict that specific striatal malfunctions can contribute to either impaired or enhanced selection, and provide clues to solving the paradox of how Huntington\'s disease can lead to both impaired and enhanced cognitive processes.