The detection and measurement of locomotor deficits in a transgenic mouse model of Huntington's disease are task- and protocol-dependent: Influence of non-motor factors on locomotor function

Pallier, Patrick N.; Drew, Cheney; Morton, A. Jennifer

doi:10.1016/j.brainresbull.2008.10.007

Cited by 60 publications

(45 citation statements)

References 47 publications

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“…The climbing assay did not prove to be reliable or sensitive over the course of the R6/2 lifespan. Only some of the measurements observed in the climbing test tracked disease progression, consistent with previous reports (Hickey et al, 2005;Menalled et al, 2009;Pallier et al, 2009). The climbing test failed to distinguish between genotypes because all mice reduced their activity in parallel over repeated tests.…”

Section: A Single Behavioral Test Was Insufficient To Monitor Diseasesupporting

confidence: 90%

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Cortical Metabolites as Biomarkers in the R6/2 Model of Huntington's Disease

Zacharoff

Tkáč

Song³

et al. 2011

J Cereb Blood Flow Metab

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To improve the ability to move from preclinical trials in mouse models of Huntington's disease (HD) to clinical trials in humans, biomarkers are needed that can track similar aspects of disease progression across species. Brain metabolites, detectable by magnetic resonance spectroscopy (MRS), have been suggested as potential biomarkers in HD. In this study, the R6/2 transgenic mouse model of HD was used to investigate the relative sensitivity of the metabolite profiling and the brain volumetry to anticipate the disease progression. Magnetic resonance imaging (MRI) and 1 H MRS data were acquired at 9.4 T from the R6/2 mice and wild-type littermates at 4, 8, 12, and 15 weeks. Brain shrinkage was detectable in striatum, cortex, thalamus, and hypothalamus by 12 weeks. Metabolite changes in cortex paralleled and sometimes preceded those in striatum. The entire set of metabolite changes was compressed into principal components (PCs) using Partial Least Squares-Discriminant Analysis (PLS-DA) to increase the sensitivity for monitoring disease progression. In comparing the efficacy of volume and metabolite measurements, the cortical PC1 emerged as the most sensitive single biomarker, distinguishing R6/2 mice from littermates at all time points. Thus, neurochemical changes precede volume shrinkage and become potential biomarkers for HD mouse models.

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Section: A Single Behavioral Test Was Insufficient To Monitor Diseasesupporting

confidence: 90%

“…Mice had no motivation to climb other than endogenous curiosity. Combined, multiple behavioral tests with strong motivational aspects may be needed to construct a reliable, repeatable behavioral biomarker (Pallier et al, 2009). …”

Section: A Single Behavioral Test Was Insufficient To Monitor Diseasementioning

confidence: 99%

Cortical Metabolites as Biomarkers in the R6/2 Model of Huntington's Disease

Zacharoff

Tkáč

Song³

et al. 2011

J Cereb Blood Flow Metab

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“…There was no significant difference in the total distance travelled by C-section-delivered or asphyxiated offspring in the open field at any postnatal age examined, suggesting the absence of gross motor deficits in the asphyxiated offspring. However, the need for several types of tests to assess locomotor abilities has been previously documented in mice due to the nonmotor influences such as motivation, fatigue and higher cognitive functions [20] . Vestibulomotor tests assess finemotor coordination -the 'runged' rotarod is an example of one such test for use in mice [21] -but this also has a cognitive component, as the animals may learn how to best perform the task.…”

Section: Discussionmentioning

confidence: 99%

Neuropathology and Functional Deficits in a Model of Birth Asphyxia in the Precocial Spiny Mouse <i>(Acomys cahirinus)</i>

Hutton

Ratnayake²,

Shields

et al. 2009

Dev Neurosci

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Birth asphyxia can result in sensory impairment, learning and memory deficits without gross brain injury and severe motor deficits. We developed a model of birth asphyxia resulting in mild neurological injury and cognitive impairment using a long-gestation species with precocial fetal development. Spiny mice (Acomys cahirinus) underwent caesarean-section delivery or 7.5 min of asphyxia at 37 days gestational age (term is 39 days). Brain histology was examined at 1 and 7 days of age, and behaviour was evaluated to 28 days of age. Asphyxiated offspring showed significant impairment in non-spatial memory and learning tasks, accompanied by central nervous system inflammation and increased apoptotic cell death but without the presence of large necrotic or cystic lesions.

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“…These differences were not immediately discernible in the Npc1 +/-mice by visual inspection, but were detected using a sensitive computer-assisted locomotor array in the open-field +/+ mice, demonstrating an increase in stride length and duration concomitant with decreased stride frequency. This is a surprising result, as animals with cerebellar ataxia usually present with decreased stride length and duration accompanied by an increase in stride frequency [31,34,35]. Given that Npc1 +/-mice presented with an intermediate voluntary movement phenotype, we expected these mice to also have moderate gait abnormalities.…”

Section: Discussionmentioning

confidence: 98%

“…To appraise gait parameters sensitively, we examined the mice with the DigiGait motorized treadmill system [30][31][32]. This is a forced locomotor test, which can be used to highlight gait abnormalities not detectable in a voluntary locomotor test.…”

Section: Npc1mentioning

confidence: 99%

Neurological Dysfunction in Early Maturity of a Model for Niemann–Pick C1 Carrier Status

et al. 2016

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Autosomal recessive inheritance of NPC1 with loss-of-function mutations underlies Niemann-Pick disease, type C1 (NP-C1), a lysosomal storage disorder with progressive neurodegeneration. It is uncertain from limited biochemical studies and patient case reports whether NPC1 haploinsufficiency can cause a partial NP-C1 phenotype in carriers. In the present study, we examined this possibility in heterozygotes of a natural loss-of-function mutant Npc1 mouse model. We found partial motor dysfunction and increased anxiety-like behavior in Npc1 +/-mice by 9 weeks of age.

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The detection and measurement of locomotor deficits in a transgenic mouse model of Huntington's disease are task- and protocol-dependent: Influence of non-motor factors on locomotor function

Cited by 60 publications

References 47 publications

Cortical Metabolites as Biomarkers in the R6/2 Model of Huntington's Disease

Cortical Metabolites as Biomarkers in the R6/2 Model of Huntington's Disease

Neuropathology and Functional Deficits in a Model of Birth Asphyxia in the Precocial Spiny Mouse <i>(Acomys cahirinus)</i>

Neurological Dysfunction in Early Maturity of a Model for Niemann–Pick C1 Carrier Status

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