Locomotor analysis identifies early compensatory changes during disease progression and subgroup classification in a mouse model of amyotrophic lateral sclerosis.

Autor:	Haulcomb MM; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN; Research and Development Service, Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA., Meadows RM; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN; Research and Development Service, Roudebush Veterans Administration Medical Center, Indianapolis, IN; Program in Medical Neurosciences, Indiana University School of Medicine, Indianapolis, IN, USA., Miller WM; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN; Research and Development Service, Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA., McMillan KP; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN; Research and Development Service, Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA., Hilsmeyer MJ; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA., Wang X; Department of Statistics, Indiana University, Bloomington, IN, USA., Beaulieu WT; Department of Statistics, Indiana University, Bloomington, IN, USA., Dickinson SL; Department of Statistics, Indiana University, Bloomington, IN; Department of Epidemiology and Biostatistics, Indiana University, Bloomington, IN, USA., Brown TJ; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN; Research and Development Service, Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA., Sanders VM; Department of Cancer Biology and Genetics, The Ohio State University Wexner Medical Center, Columbus, OH, USA., Jones KJ; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN; Research and Development Service, Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA.
Jazyk:	angličtina
Zdroj:	Neural regeneration research [Neural Regen Res] 2017 Oct; Vol. 12 (10), pp. 1664-1679.
DOI:	10.4103/1673-5374.217346
Abstrakt:	Amyotrophic lateral sclerosis is a motoneuron degenerative disease that is challenging to diagnose and presents with considerable variability in survival. Early identification and enhanced understanding of symptomatic patterns could aid in diagnosis and provide an avenue for monitoring disease progression. Use of the mSOD1G93A mouse model provides control of the confounding environmental factors and genetic heterogeneity seen in amyotrophic lateral sclerosis patients, while investigating underlying disease-induced changes. In the present study, we performed a longitudinal behavioral assessment paradigm and identified an early hindlimb symptom, resembling the common gait abnormality foot drop, along with an accompanying forelimb compensatory mechanism in the mSOD1G93A mouse. Following these initial changes, mSOD1 mice displayed a temporary hindlimb compensatory mechanism resembling an exaggerated steppage gait. As the disease progressed, these compensatory mechanisms were not sufficient to sustain fundamental locomotor parameters and more severe deficits appeared. We next applied these initial findings to investigate the inherent variability in B6SJL mSOD1G93A survival. We identified four behavioral variables that, when combined in a cluster analysis, identified two subpopulations with different disease progression rates: a fast progression group and a slow progression group. This behavioral assessment paradigm, with its analytical approaches, provides a method for monitoring disease progression and detecting mSOD1 subgroups with different disease severities. This affords researchers an opportunity to search for genetic modifiers or other factors that likely enhance or slow disease progression. Such factors are possible therapeutic targets with the potential to slow disease progression and provide insight into the underlying pathology and disease mechanisms. Competing Interests: We have no conflict of interests
Databáze:	MEDLINE
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