Jenny Morton

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..The significance of these findings is discussed in the context of the R6/2 mouse as a model for HD...

..Sheep have great potential, not only for use as a large animal model of HD, but also for studying cognitive function and the evolution of complex behaviours in normal animals...

..Our study shows that cognitive decline caused by a genetic mutation can be slowed by a combination drug treatment, and gives hope that cognitive symptoms in HD can be treated...

..Our results suggest that changes in neurotransmitter release might contribute to the neuronal dysfunction seen in these mice...

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..We propose that circadian sleep disturbances are an important pathological feature of HD, that they arise from pathology within the SCN molecular oscillation, and that their treatment will bring appreciable benefits to HD patients...

..This mouse may represent a better model for adult-onset HD than R6/2 mice with shorter repeats...

..Given that decreased expression of CPLXII is seen in HD and schizophrenic patients, a role for CPLXII depletion should be considered in other diseases where motor, cognitive and psychiatric symptoms co-exist...

..These results support the idea that altered expression of complexins in disease states may contribute to the symptomatology of disorders in which they are dysregulated...

..These results suggest that dysfunctional DA neurotransmission contributes to phenotype development in R6/2 mice and thus also may be important in symptom progression in HD...

..These results suggest that olfactory impairments observed in HD patients may be the result of reduced plasticity in the primary olfactory cortex...

..We suggest that downregulation of expression of mRNA encoding SNARE-associated proteins, first CPLXII and later CPLXI and alpha-SNAP, contributes to the progressive neuropathology of the R6/2 mouse model of Huntington's disease...

..Their role in the pathogenesis of HD is likely to depend on their location as well as their composition...

..We conclude that following striatal decline in R6/2 mice between 8 and 12 weeks of age, hippocampal functions emerge to drive the escape response of R6/2 mice...

..Thus, even subtle imbalances in liver function may exacerbate symptoms of HD, where neurological function is already compromised...

..Abnormalities in complexin 1 levels in the brain may therefore contribute to the psycho-social aspects of human diseases in which this protein is dysregulated...

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..We suggest that this is due to the inability of Congo red to cross the blood-brain barrier. Since it does not improve the behavioural deterioration that is a key feature of HD, Congo red is unlikely to be useful as a therapy for HD...

..The existence of similar compensatory mechanisms may explain why, in humans, HD is a late-onset disorder, despite early expression of the genetic mutation...

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..This impairment in MF LTP could contribute to spatial learning deficits observed in R6/2 and Cplx2-/- mice...

..A role for complexin I depletion should be considered in diseases where deficits in early sensory and motor development exist, such as autism and schizophrenia...

..We suggest that degenerative changes in axons are likely to contribute to the early pathological phenotype in HD, even in the absence of frank neuronal cell loss...

..We suggest that focused management of sleep and wakefulness will slow the progression of cognitive decline and apathy in neurological conditions where sleep is disordered...

..Complexin II depletion in the brain may account for some of the abnormalities in neurotransmission associated with HD...

..Together, our data suggest a central role for CaN in the deleterious phenotype of the R6/2 mouse. Treatments aimed at preventing the loss of CaN or stimulating its function may be beneficial in the treatment of HD...

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..The temporal and regional changes in synaptic plasticity within the hippocampus mirror the appearance of neuronal intranuclear inclusions, suggesting a relationship between polyglutamine aggregation and dysfunction...

..We suggest that increased thirst may be an important and clinically relevant biomarker for the study of disease progression in HD...

..However, chronic treatment with these hypoglycaemic agents had no effect on either the course of the diabetes or the disease in R6/2 mice...

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..As dopamine-dependent plasticity is a proposed model of striatum-based motor and cognitive functions, this impairment could contribute to deficits seen in R6/2 mice...

..These data indicate that VBM will be a valuable technique for in vivo measurement of developing pathology in HD transgenic mice, and may be particularly useful for correlating histologically undetectable changes with behavioral deficits...

..Having obtained proof-of-principle for the technique using ex vivo tissue, it is now our intention to carry out in vivo measurement of developing pathology in HD transgenic mice, and correlate this with behavioral deficits...

..We have also shown previously that HD patients and R6/2 mice have disrupted circadian rhythms, treatment of which may improve cognition, general health, and survival...

..These results suggest that although marked changes in sleep architecture are present in early HD and can be detected using polysomnography, patients do not necessarily recognize or report these abnormalities...

..Taken together, these experiments served to optimize the touchscreen method and have demonstrated its usefulness as a high-throughput method for the cognitive testing of rodents...

..The improvement in rotarod performance suggests that lithium may improve motor symptoms as well as depression in some HD patients...

..The reason for this is not known but may reflect a catabolic state secondary to hypothalamic pathology, as abnormalities have been reported in the hypothalamus early in the disease course...

..These results suggest that abnormal neurogenesis in the R6/2 mouse is not attributable to an intrinsic impairment of the NPC itself but is attributable to the environment in which the cell is located...

..This indicates that loss of complexin II is part of the mechanism underlying the R6/2 phenotype. Whether it is causal or compensatory remains to be determined...

..These results support the possibility that impaired neurogenesis and/or plasticity could contribute to cognitive and psychiatric impairments in Huntington's disease...

..Further, social and emotional memories appear to be encoded in a rigid way that is not influenced by subsequent learning or by arousal levels...

..Together our data are compatible with a toxic role for aggregates/aggregation and support the 'toxic precursor' hypothesis. However, they also suggest that at some stages, the process of aggregate formation is cytoprotective...

..A greater increase in reactive gliosis was also seen after exposure to METH and loud music. Thus, METH appears to be more toxic when taken while exposed to loud music...

..It appears likely that ETs play an important neuromodulatory role in the cerebellum...

..We conclude that syncollin is required for efficient exocytosis in the pancreatic acinar cell, and that it plays a particularly important role in compound exocytosis...

..Such changes in the dynamic status of microglia may lead to an impairment of their neurosupportive functions. Further studies are needed to understand better the role of microglia in aging and neurodegeneration...

..Together, these data demonstrate that weight loss in R6/2 mice is associated with increased metabolism and changes in several weight-regulating factors...

..However, irrespective of the cause, the abnormalities at neuromuscular junctions we report here are likely to contribute to the pathological phenotype in R6/2 mice, particularly in late stages of the disease...