A5071711769- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Neurological disorders and treatments
- Circadian rhythm and melatonin
- Muscle Physiology and Disorders
- Sleep and Wakefulness Research
- Ion channel regulation and function
- Neurogenesis and neuroplasticity mechanisms
- Receptor Mechanisms and Signaling
- Parkinson's Disease Mechanisms and Treatments
- Memory and Neural Mechanisms
- Nitric Oxide and Endothelin Effects
- Cellular transport and secretion
- Neural dynamics and brain function
- Neurotransmitter Receptor Influence on Behavior
- Neuroinflammation and Neurodegeneration Mechanisms
- Nerve injury and regeneration
- Sleep and related disorders
- RNA Research and Splicing
- Primate Behavior and Ecology
- Alzheimer's disease research and treatments
- Marine and fisheries research
- Ubiquitin and proteasome pathways
- Cell Image Analysis Techniques
University of Cambridge
2015-2024
Google (United States)
2017
Bridge University
2010
Addenbrooke's Hospital
1987-2008
Lawn Tennis Association
2003
Babraham Institute
1990-1995
Biotechnology and Biological Sciences Research Council
1992
University of Otago
1985-1987
Transgenic mice expressing exon 1 of the human Huntington's disease (HD) gene carrying a 141-157 CAG repeat (line R6/2) develop progressive neurological phenotype with motor symptoms resembling those seen in HD. We have characterized deficits R6/2 using battery behavioral tests selected to measure aspects swimming, fore- and hindlimb coordination, balance, sensorimotor gating [swimming tank, rotarod, raised beam, hindpaw footprinting, acoustic startle/prepulse inhibition (PPI)]. Behavioral...
Huntington's disease (HD) is an autosomal dominant progressive and fatal neurodegenerative brain disorder caused by expanded CAG/polyglutamine repeat in the coding region of gene. Presymptomatic patients often exhibit cognitive deficits before onset classical symptoms. To investigate possibility that changes synaptic plasticity might underlie impairment HD, we examined hippocampal spatial cognition a transgenic mouse (R6/2 line) expressing exon 1 human gene containing CAG repeat. This...
Sleep disturbances in neurological disorders have a devastating impact on patient and carer alike. However, their pathological origin is unknown. Here we show that patients with Huntington's disease (HD) disrupted night-day activity patterns. This disruption was mirrored transgenic model of HD (R6/2 mice) which daytime increased nocturnal fell, eventually leading to the complete disintegration circadian behavior. The behavioral disturbance accompanied by marked expression clock genes mPer2...
Cognitive decline is apparent in the early stages of Huntington's disease and progressively worsens throughout course disease. Expression human mutation mice (R6/2 line) causes a progressive neurological phenotype with motor symptoms resembling those seen Here we describe cognitive performance R6/2 using four different tests (Morris water maze, visual cliff avoidance, two-choice swim tank, T-maze). Behavioral testing was performed on transgenic their wild-type littermates between 3 14.5...
The touchscreen testing method for rodents is a computer-automated behavioral that allows computer graphic stimuli to be presented and the respond screen via nose-poke directly stimulus. advantages of this are numerous; however, systematic study parameters affect learning has not yet been conducted. We therefore sought optimize task in method. found when were optimized, Lister Hooded rats could learn rapidly using method, solving discrimination two-dimensional level 80% within five six...
Transgenic R6/2 mice carrying the Huntington's disease (HD) mutation show disrupted circadian rhythms that worsen as progresses. By 15 weeks of age, their abnormal behavior mirrors seen in HD patients and is accompanied by dysregulated clock gene expression pacemaker, suprachiasmatic nucleus (SCN). We found, however, electrophysiological output SCN assayed vitro was normal. Furthermore, endogenous rhythm expression, monitored luciferase imaging organotypical slices removed from with...
Behavioral circadian rhythms disintegrate progressively in the R6/2 mouse model of Huntington's disease (HD), recapitulating sleep–wake disturbance seen HD patients. Here we show that disturbances pacemaking are not restricted to brain, but also encompass peripheral metabolic pathways mice. Notably, clock-driven genes key outputs liver abolished vivo . This deficiency is accompanied by arrhythmic expression clock Cry1 and Dbp , a phase-advanced Per2 cycle. Compromised cycles not, however,...
Abstract Huntington's disease (HD) is a neurodegenerative disorder with complex symptoms dominated by progressive motor dysfunction. Skeletal muscle atrophy common in HD patients. Because the mutation expressed skeletal as well brain, we wondered whether changes arise from primary pathology. We used R6/2 transgenic mice for our studies. Unlike denervation atrophy, occurs uniformly. Paradoxically however, muscles show age‐dependent denervation‐like abnormalities, including supersensitivity to...
Huntington's disease (HD) is an autosomal dominant neurodegenerative condition characterized by movement disorders, psychiatric disturbance, and cognitive decline. There are no treatments to halt or reverse the disease. Mammalian neurogenesis persists into adulthood in subventricular zone (SVZ) dentate gyrus (DG) of hippocampus. In 2001, our laboratory published hypothesis that impaired diseases this may contribute progression. Since then, it has been shown reduced DG transgenic HD mice but...
Huntington's disease (HD) is a fatal neurodegenerative caused by genetic expansion of the CAG repeat region in huntingtin (HTT) gene. Studies HD mouse models have shown that artificial miRNAs can reduce mutant HTT, but evidence for their effectiveness and safety larger animals lacking. transgenic sheep express full-length human HTT with 73 repeats. AAV9 was used to deliver unilaterally striatum an miRNA targeting exon 48 mRNA under control two alternative promoters: U6 or CβA. The treatment...
One of the most important human social skills is ability to recognize faces. Humans familiar faces easily, and can learn identify unfamiliar from repeatedly presented images. Sheep are animals that other sheep as well humans. Little known, however, about their holistic face-processing abilities. In this study, we trained eight ( Ovis aries ) four celebrities photographic portraits displayed on computer screens. After training, chose ‘learned-familiar’ rather than significantly above chance....