Abstract

The automatization of behavioral tests assessing motor activity in rodent models is important for providing robust and reproducible results and evaluating new therapeutics. The CatWalk system is an observer-independent, automated and computerized technique for the assessment of gait performance in rodents. This method has previously been used in adult rodent models of CNS-based movement disorders such as Parkinson’s and Huntington’s diseases. As motor and gait abnormalities in neuropsychiatric disorders are observed during infancy and adolescence, it became important to validate the CatWalk XT in the gait analysis of adolescent mice and unravel factors that may cause variations in gait performance. Three adolescent wild-type inbred mouse strains, C57BL/6N, DBA/2 and FVB/N, were tested using the CatWalk XT (Version 10.6) for suitable detection settings to characterize several gait parameters at P32 and P42. The same detection settings being suitable for C57BL/6N and DBA/2 mice allowed a direct comparison between the two strains. On the other hand, due to their increased body weight and size, FVB/N mice required different detection settings. The CatWalk XT reliably measured the temporal, spatial, and interlimb coordination parameters in the investigated strains during adolescence. Additionally, significant effects of sex, development, speed and body weight within each strain confirmed the sensitivity of motor and gait functions to these factors. The CatWalk gait analysis of rodents during adolescence, taking the effect of age, strain, sex, speed and body weight into consideration, will decrease intra-laboratory discrepancies and increase the face validity of rodent models of neuropsychiatric disorders.

Highlights

  • Motor and coordination dysfunctions including gait abnormalities are the main diagnostic criteria for many CNS disorders such as Parkinson’s, Huntington’s and Alzheimer’s diseases, amyotrophic lateral sclerosis, and stroke

  • Most of the gait parameters that we focused on in our study are shown for each paw, namely the left front (LF), left hind (LH), right front (RF), and right hind (RH) paw

  • The body weights of mice was used as an indicator of their general condition, a guide for determining suitable detection settings, and to find its correlation to different gait parameters

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Summary

Introduction

Motor and coordination dysfunctions including gait abnormalities are the main diagnostic criteria for many CNS disorders such as Parkinson’s, Huntington’s and Alzheimer’s diseases, amyotrophic lateral sclerosis, and stroke (for reviews, ­see[1,2,3,4,5,6,7,8,9,10,11]). Qualitative and quantitative behavioral experiments of motor deficits including the rotarod, grip strength, inverted screen, and beam balance rod tests are often used in rodent models based on the wide range of parallels between rodents and human locomotion These assays are a quantifiable measure of the effectiveness of various therapeutic strategies. We examined the ability of adolescent mice from three wild-type inbred strains, C57BL/6N, DBA/2 and FVB/N, to perform several behavioral tests assessing motor and coordination function including the inverted screen, cliff avoidance reaction, rotarod, and voluntary wheel running ­tests[41]. Our study provides useful insights for behavioral experimental designs and presents reference data on gait performance when using young mice for preclinical investigations in neuropsychiatric indications

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