Delaying the onset of Huntington's in mice

Dellen, Anton van; Blakemore, Colin; Deacon, Robert M. J.; York, Denis; Hannan, Anthony J.

doi:10.1038/35008142

Cited by 470 publications

(335 citation statements)

References 12 publications

Supporting

Mentioning

310

Contrasting

Unclassified

Order By: Relevance

“…Two independent groups have analyzed the effect of an increased environmental stimulation on the phenotype and neuropathology of R6 mice van Dellen et al, 2000;Hockly et al, 2002;Glass et al, 2004;Spires et al, 2004). These studies have demonstrated that the exposure of R6/1 (van Dellen et al, 2000;Glass et al, 2004;Spires et al, 2004) or R6/2 (Hockly et al, 2002) mice to an enriched environment (consisting of large standard cages with cardboard, paper and plastic objects, which were changed every two to three times per week) delayed the onset of motor symptoms, decreased the severity of the clasping phenotype, and reduced the loss of the peristriatal cerebral volume. Carter et al (2000) also demonstrated that, improving the access to food and water had beneficial effects.…”

Section: Environmental Enrichmentmentioning

confidence: 99%

The R6 lines of transgenic mice: A model for screening new therapies for Huntington's disease

Gil

Rego

2009

Brain Research Reviews

View full text Add to dashboard Cite

Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an expanded CAG repeat in the HD gene that results in cortical and striatal degeneration, and mutant huntingtin aggregation. Current treatments are unsatisfactory. R6 transgenic mice replicate many features of the human condition, show early onset of symptoms and fast disease progression, being one of the most used models for therapy screening. Here we review the therapies that have been tested in these mice: environmental enrichment, inhibition of histone deacetylation and methylation, inhibition of misfolding and oligomerization, transglutaminase inhibition, rescue of metabolic impairment, amelioration of the diabetic phenotype, use of antioxidants, inhibition of excitotoxicity, caspase inhibition, transplantation, genetic manipulations, and restoration of neurogenesis. Although many of these treatments were beneficial in R6 mice, they may not be as effective in HD patients, and thus the search for a combination of therapies that will rescue the human condition continues.

show abstract

Section: Environmental Enrichmentmentioning

confidence: 99%

The R6 lines of transgenic mice: A model for screening new therapies for Huntington's disease

Gil

Rego

2009

Brain Research Reviews

View full text Add to dashboard Cite

show abstract

“…The beneficial effects of environmental enrichment in rodent cognitive and motor performance are well known (van Praag et al, 2000). In the HD field, numerous studies using R6/2 and R6/1 also have shown that offering even minimally-enriched living conditions (e.g., providing group-housed animals with a play tunnel) improves the animals' performance and promotes the survival of the mutant mice (Carter et al, 2000;Hockly et al, 2002;van Dellen et al, 2000;van Dellen et al, 2008). Since the goal is to find robust therapeutic agents, we recommend maintaining the animals under group-housed conditions with a moderate level of enrichment (e.g., play tunnel, plastic bone and shredded paper) for preclinical testing purposes.…”

Section: Iii1 Littersmentioning

confidence: 99%

Mouse models of Huntington's disease

Menalled¹,

Chesselet²

2002

Trends in Pharmacological Sciences

264

157

View full text Add to dashboard Cite

“…Results obtained from mouse models of neurodegenerative disease show that environmental enrichment or voluntary exercise is beneficial in terms of delayed onset and progression of disease (17)(18)(19)(20). Investigators modeled human physical, social, and intellectual enrichment by placing at least two animals in large cages with running wheels, toys, and colorful tunnels (21).…”

mentioning

confidence: 99%

Exercise reverses preamyloid oligomer and prolongs survival in αB-crystallin-based desmin-related cardiomyopathy

Maloyan

Gulick

Glabe

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The R120G mutation in the small heat shock-like protein ␣B-crystallin (CryAB R120G ) causes desmin-related myopathy (DRM), which is characterized by the formation of desmin-and CryABcontaining aggregates within muscle fibers. Mice with cardiacspecific overexpression of CryAB R120G develop cardiomyopathy at 3 months and die at 6 -7 months from heart failure (HF). Previous studies showed that overexpression of CryAB R120G results in accumulation of preamyloid oligomer (PAO). PAO is considered to be the cytotoxic entity in many of the protein misfolding-based neurodegenerative diseases. On the basis of data from mouse models of neurodegenerative diseases showing that exercise or environmental enrichment reduces the amyloid oligomer level and improves cognitive ability, we hypothesized that CryAB R120G -induced DRM would also respond favorably to prolonged voluntary exercise, reducing HF symptoms and rescuing the mice from premature death. Six months of voluntary exercise in CryAB R120G animals resulted in 100% survival at a time when all unexercised mice had died. After 22 weeks of exercise, PAO levels were decreased by 47% compared with the unexercised CryAB R120G control mice (P ‫؍‬ 0.00001). Although CryAB R120G expression led to decreased levels of the metallomembrane endopeptidase neprilysin, normal levels were maintained in the exercised CryAB R120G mice, and in vitro loss-of-function and gain-of-function experiments using adenovirus-infected cardiomyocytes confirmed the importance of neprilysin in ameliorating PAO accumulation. The data demonstrate that voluntary exercise slows the progression to HF in the CryAB R120G DRM model and that PAO accumulation is mediated, at least in part, by decreased neprilysin activity.cardiac ͉ disease ͉ heart ͉ transgenic

show abstract

Delaying the onset of Huntington's in mice

Cited by 470 publications

References 12 publications

The R6 lines of transgenic mice: A model for screening new therapies for Huntington's disease

The R6 lines of transgenic mice: A model for screening new therapies for Huntington's disease

Mouse models of Huntington's disease

Exercise reverses preamyloid oligomer and prolongs survival in αB-crystallin-based desmin-related cardiomyopathy

Contact Info

Product

Resources

About