'Super-Enrichment' Reveals Dose-Dependent Therapeutic Effects of Environmental Stimulation in a Transgenic Mouse Model of Huntington's Disease.

Background: Huntington's disease (HD) is caused by a tandem repeat expansion and involves progressive cognitive decline, psychiatric abnormalities and motor deficits. Disease onset and progression in HD mice can be substantially delayed by a housing environment with enhanced sensorimotor and cognitive stimulation. However, the proposed benefits of environmental enrichment (EE) are always taken in the context of 'deprived' standard housing and investigation is warranted into the graded effects of enrichment.

Environmental enrichment reduces neuronal intranuclear inclusion load but has no effect on messenger RNA expression in a mouse model of Huntington disease.

Huntington disease (HD) is a fatal neurodegenerative disease with no effective treatment. In the R6/1 mouse model of HD, environmental enrichment delays the neurologic phenotype onset and prevents cerebral volume loss by unknown molecular mechanisms. We examined the effects of environmental enrichment on well-characterized neuropathological parameters in a mouse model of HD.

Wheel running from a juvenile age delays onset of specific motor deficits but does not alter protein aggregate density in a mouse model of Huntington's disease.

Background: Huntington's disease (HD) is a neurodegenerative disorder predominantly affecting the cerebral cortex and striatum. Transgenic mice (R6/1 line), expressing a CAG repeat encoding an expanded polyglutamine tract in the N-terminus of the huntingtin protein, closely model HD. We have previously shown that environmental enrichment of these HD mice delays the onset of motor deficits.

Olfactory abnormalities in Huntington's disease: decreased plasticity in the primary olfactory cortex of R6/1 transgenic mice and reduced olfactory discrimination in patients.

Reduced neuronal plasticity in the striatum, hippocampus, and neocortex is a common feature of transgenic mouse models of Huntington's disease (HD). Doublecortin (DCX) and polysialylated neural cell adhesion molecule (PSA-NCAM) are associated with structural plasticity in the adult mammalian brain, are markers of newly formed neurons in the dentate gyrus of the adult hippocampus, and are highly expressed in primary olfactory (piriform) cortex. Animal studies have demonstrated that a reduction in plasticity in the piriform cortex is associated with a selective impairment in odour discrimination.

Stroke as a clinical emergency.

Figures from the National Audit Office ( 2005 ) reveal that stroke accounts for 11 per cent of deaths in England and Wales each year, that up to 30 per cent of stroke patients die within a month of event, and that a quarter of people living to the age of 85 can expect to have a stroke.

Neurogenesis in the R6/1 transgenic mouse model of Huntington's disease: effects of environmental enrichment.

Previous work has demonstrated that the transgenic R6/1 mouse model of Huntington's disease has decreased proliferation of neural precursor cells (NPCs) in the dentate gyrus of the hippocampus. This study therefore examined the survival and differentiation of NPCs in presymptomatic and symptomatic R6/1 mice and the effects of environmental enrichment on these variables. Here it is demonstrated that the survival of bromodeoxyuridine-positive (BrdU+) NPCs in the dentate gyrus is decreased in the transgenic mice.

Gene-environment interactions, neuronal dysfunction and pathological plasticity in Huntington's disease.

Huntington's disease (HD) is a fatal autosomal dominant disorder in which there is progressive neurodegeneration producing motor, cognitive and psychiatric symptoms. The dynamic mutation that causes the disease is common to numerous other brain disorders, which may share similar pathogenic mechanisms. Much progress has been made in the past decade in understanding how a trinucleotide (CAG) repeat expansion, encoding an expanded polyglutamine tract in the huntingtin protein, induces dysfunction at molecular and cellular levels.

Cognitive disorders and neurogenesis deficits in Huntington's disease mice are rescued by fluoxetine.

Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat encoding an extended polyglutamine tract in the huntingtin protein. Affected individuals display progressive motor, cognitive and psychiatric symptoms (including depression), leading to terminal decline. Given that transgenic HD mice have decreased hippocampal cell proliferation and that a deficit in neurogenesis has been postulated as an underlying cause of depression, we hypothesized that decreased hippocampal neurogenesis contributes to depressive symptoms and cognitive decline in HD.

Use of an impedance threshold device improves short-term outcomes following out-of-hospital cardiac arrest.

Introduction: An impedance threshold device (ITD) has been developed for the treatment of cardiac arrest to augment circulation to the heart and brain during cardiopulmonary resuscitation (CPR). The ITD has ventilation timing lights that flash at 12 min(-1) to discourage excessive ventilation rates.

Hypothesis: Implementation of the ITD during conventional manual CPR in a large emergency medical services (EMS) system (Staffordshire, UK) is safe, feasible and will improve short-term survival.

Deficits in experience-dependent cortical plasticity and sensory-discrimination learning in presymptomatic Huntington's disease mice.

Huntington's disease (HD) is one of a group of neurodegenerative diseases caused by an expanded trinucleotide (CAG) repeat coding for an extended polyglutamine tract. The disease is inherited in an autosomal dominant manner, with onset of motor, cognitive, and psychiatric symptoms typically occurring in midlife, followed by unremitting progression and eventual death. We report here that motor presymptomatic R6/1 HD mice show a severe impairment of somatosensory-discrimination learning ability in a behavioral task that depends heavily on the barrel cortex.

Impaired learning-dependent cortical plasticity in Huntington's disease transgenic mice.

Huntington's disease (HD) is a genetically transmitted neurodegenerative disorder. The neuropathology in HD is a selective neuronal cell death in several brain regions including cortex. Although changes in synaptic plasticity were shown within the hippocampus and striatum of HD transgenic mice, there are no studies considering neocortical synaptic plasticity abnormalities in HD.

Dendritic spine pathology and deficits in experience-dependent dendritic plasticity in R6/1 Huntington's disease transgenic mice.

Huntington's disease (HD) is a fatal neurodegenerative disease caused by a CAG repeat expansion coding for an expanded polyglutamine tract in the huntingtin protein. Dendritic abnormalities occur in human HD patients and in several transgenic mouse models of the disease. In this study, we examine, for the first time, dendrite and spine pathology in the R6/1 mouse model of HD, which mimics neurodegeneration seen in human HD.

Decreased hippocampal cell proliferation in R6/1 Huntington's mice.

In order to ascertain whether disturbances of neurogenesis occur in chronic neurodegenerative disorders, we assessed hippocampal cell proliferation in the R6/1 transgenic mouse model of Huntington's disease (HD). Using BrdU labelling for dividing cells at two different time points (5 and 20 weeks) in transgenic and wild type control mice, we have shown that cell proliferation in the hippocampus was similar in younger asymptomatic R6/1 mice and wild type controls, but that older R6/1 mice had significantly fewer BrdU cells than controls. Such a decrease in cell proliferation may be relevant to some of the deficits seen in these mice, although further work is needed to prove this.

Environmental enrichment rescues protein deficits in a mouse model of Huntington's disease, indicating a possible disease mechanism.

Huntington's disease (HD) is a devastating neurodegenerative disorder caused by a CAG repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. Transgenic mice expressing a human huntingtin transgene containing an expanded CAG repeat (R6/1 model) develop a neurodegenerative disorder closely resembling human HD. Previous work demonstrated that environmental enrichment delays the onset of motor symptoms in this mouse model.

Genetic and environmental factors in the pathogenesis of Huntington's disease.

Huntington's disease is a fatal inherited disorder in which there is progressive neurodegeneration in specific brain areas, mainly the striatum and cerebral cortex, producing motor, cognitive, and psychiatric symptoms. The trinucleotide repeat mutation involved is common to many other brain diseases, which may therefore involve similar mechanisms of pathogenesis. We are beginning to understand how a CAG trinucleotide repeat expansion in the disease gene, encoding an expanded polyglutamine tract, induces neuronal dysfunction and symptomatology in Huntington's disease.

Environmental enrichment slows disease progression in R6/2 Huntington's disease mice.

Huntington's disease is a genetic disorder that causes motor dysfunction, personality changes, dementia, and premature death. There is currently no effective therapy. Several transgenic models of Huntington's disease are available, the most widely used of which is the R6/2 mouse, because of its rapid disease progression.