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Huntington's disease is a fatal neurodegenerative disorder caused by an expanded polyglutamine repeat in huntingtin (HTT) protein. We previously showed that calorie restriction ameliorated Huntington's disease pathogenesis and slowed disease progression in mice that model Huntington's disease (Huntington's disease mice). We now report that overexpression of(More)
Mouse models of Huntington's disease (HD) that recapitulate some of the phenotypic features of human HD, play a crucial role in investigating disease mechanisms and testing potential therapeutic approaches. Longitudinal studies of these models can yield valuable insights into the temporal course of disease progression and the effect of drug treatments on(More)
White matter abnormalities have been reported in premanifest Huntington's disease (HD) subjects before overt striatal neuronal loss, but whether the white matter changes represent a necessary step towards further pathology and the underlying mechanism of these changes remains unknown. Here, we characterized a novel knock-in mouse model that expresses mouse(More)
Huntington's disease (HD) is a fatal neurodegenerative disease characterized by abnormal motor coordination, cognitive decline and psychiatric disorders. This disease is caused by an expanded CAG trinucleotide repeat in the gene encoding the protein huntingtin. Reduced levels of brain-derived neurotrophic factor (BDNF) in the brain, which results from(More)
Huntington's disease (HD) is caused by a polyglutamine expansion in the Huntingtin (Htt) protein. Proteolytic cleavage of Htt into toxic N-terminal fragments is believed to be a key aspect of pathogenesis. The best characterized putative cleavage event is at amino acid 586, hypothesized to be mediated by caspase 6. A corollary of the caspase 6 cleavage(More)
Sirtuin 1 is a nicotinamide adenine dinucleotide-dependent protein deacetylase which regulates longevity and improves metabolism. Activation of Sirtuin 1 confers beneficial effects in models of neurodegenerative diseases. We and others have provided convincing evidence that overexpression of Sirtuin 1 plays a neuroprotective role in mouse models of(More)
Inflammatory mechanisms mediated by prostaglandins may contribute to the progression of intracerebral hemorrhage (ICH)-induced brain injury, but they are not fully understood. In this study, we examined the effect of prostaglandin E2 receptor EP1 (EP1R) activation and inhibition on brain injury in mouse models of ICH and investigated the underlying(More)
Mouse models of human diseases play crucial roles in understanding disease mechanisms and developing therapeutic measures. Huntington's disease (HD) is characterized by striatal atrophy that begins long before the onset of motor symptoms. In symptomatic HD, striatal volumes decline predictably with disease course. Thus, imaging based volumetric measures(More)
Huntington's disease (HD) displays progressive striatal atrophy that occurs long before the onset of clinical motor symptoms. As there is no treatment for the disease once overt symptoms appear, it has been suggested that neuroprotective therapy given during this presymptomatic period might slow progression of the disease. This requires biomarkers that can(More)
OBJECTIVE Using an animal model, we have previously shown that preeclampsia results in long-term adverse neuromotor outcomes in the offspring, and this phenotype was prevented by antenatal treatment with pravastatin. This study aims to localize the altered neuromotor programming in this animal model and to evaluate the role of pravastatin in its prevention.(More)