Dataset Information

Motor Neuron Abnormalities Correlate with Impaired Movement in Zebrafish that Express Mutant Superoxide Dismutase 1.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. ALS can be modeled in zebrafish (Danio rerio) through the expression of human ALS-causing genes, such as superoxide dismutase 1 (SOD1). Overexpression of mutated human SOD1 protein causes aberrant branching and shortening of spinal motor axons. Despite this, the functional relevance of this axon morphology remains elusive. Our aim was to determine whether this motor axonopathy is correlated with impaired movement in mutant (MT) SOD1-expressing zebrafish. Transgenic zebrafish embryos that express blue fluorescent protein (mTagBFP) in motor neurons were injected with either wild-type (WT) or MT (A4V) human SOD1 messenger ribonucleic acid (mRNA). At 48 hours post-fertilization, larvae movement (distance traveled during behavioral testing) was examined, followed by quantification of motor axon length. Larvae injected with MT SOD1 mRNA had significantly shorter and more aberrantly branched motor axons (p?2?=?0.357, p?

SUBMITTER: Robinson KJ

PROVIDER: S-EPMC6357263 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Motor Neuron Abnormalities Correlate with Impaired Movement in Zebrafish that Express Mutant Superoxide Dismutase 1.

Robinson Katherine J KJ Yuan Kristy C KC Don Emily K EK Hogan Alison L AL Winnick Claire G CG Tym Madelaine C MC Lucas Caitlin W CW Shahheydari Hamideh H Watchon Maxinne M Blair Ian P IP Atkin Julie D JD Nicholson Garth A GA Cole Nicholas J NJ Laird Angela S AS

Zebrafish 20181027 1

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. ALS can be modeled in zebrafish (Danio rerio) through the expression of human ALS-causing genes, such as superoxide dismutase 1 (SOD1). Overexpression of mutated human SOD1 protein causes aberrant branching and shortening of spinal motor axons. Despite this, the functional relevance of this axon morphology remains elusive. Our aim was to determine whether this motor axonop ...[more]

PMID: 30300572

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Project description:Background and objectivesAlthough oculomotor abnormalities (OMAs) are not usually considered prominent features of amyotrophic lateral sclerosis (ALS), they may represent potential clinical markers of neurodegeneration, especially when investigated together with cognitive and behavioral alterations. The aim of our study was to identify patterns of clinically evident OMAs in patients with ALS and to correlate such findings with cognitive-behavioral data.MethodsThree consecutive inpatient cohorts of Italian patients with ALS and controls were retrospectively evaluated to assess the frequency of OMAs and cognitive-behavioral alterations. The ALS population was divided into a discovery cohort and a replication cohort. Controls included a cohort of cognitively impaired individuals and patients with Alzheimer disease (AD). Participants underwent bedside eye movement evaluation to determine the presence and pattern of OMAs. Cognitive assessment was performed with a standard neuropsychological battery (discovery ALS cohort and AD cohort) and the Italian Edinburgh Cognitive and Behavioural ALS Screen (ECAS) (replication ALS cohort).ResultsWe recruited 864 individuals with ALS (635 discovery, 229 replication), 798 who were cognitively unimpaired and 171 with AD. OMAs were detected in 10.5% of our ALS cohort vs 1.6% of cognitively unimpaired controls (p = 1.2 × 10-14) and 11.4% of patients with AD (p = NS). The most frequent deficits were smooth pursuit and saccadic abnormalities. OMA frequency was higher in patients with bulbar onset, prominent upper motor neuron signs, and advanced disease stages. Cognitive dysfunction was significantly more frequent in patients with OMAs in both ALS cohorts (p = 1.1 × 10-25). Furthermore, OMAs significantly correlated with the severity of cognitive impairment and with pathologic scores at the ECAS ALS-specific domains. Last, OMAs could be observed in 35.0% of cognitively impaired patients with ALS vs 11.4% of patients with AD (p = 6.4 × 10-7), suggesting a possible involvement of frontal oculomotor areas in ALS.ConclusionPatients with ALS showed a range of clinically evident OMAs, and these alterations were significantly correlated with cognitive, but not behavioral, changes. OMAs may be a marker of neurodegeneration, and bedside assessment represents a rapid, highly specific tool for detecting cognitive impairment in ALS.

Dataset Information

Motor Neuron Abnormalities Correlate with Impaired Movement in Zebrafish that Express Mutant Superoxide Dismutase 1.

Publications

Motor Neuron Abnormalities Correlate with Impaired Movement in Zebrafish that Express Mutant Superoxide Dismutase 1.

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