Four-parameter analysis in modified Rotarod test for detecting minor motor deficits in mice.
Locomotion
Neurological disorders
Rotarod test
Traumatic brain injury
Journal
BMC biology
ISSN: 1741-7007
Titre abrégé: BMC Biol
Pays: England
ID NLM: 101190720
Informations de publication
Date de publication:
17 08 2023
17 08 2023
Historique:
received:
18
04
2023
accepted:
10
08
2023
medline:
21
8
2023
pubmed:
18
8
2023
entrez:
17
8
2023
Statut:
epublish
Résumé
The Rotarod test with commercial apparatus is widely used to assess locomotor performance, balance and motor learning as well as the deficits resulting from diverse neurological disorders in laboratory rodents due to its simplicity and objectivity. Traditionally, the test ends when rodents drop from the accelerating, turning rod, and the only parameter used commonly is "latency to fall". The values of individual animals can often vary greatly. In the present study, we established a procedure for mice with 4 consecutive days of training with 4 trials per day and modified the testing procedure by placing the mice back on the rod repeatedly after each fall until the trial ends (5 min). Data from the fourth training day as baseline results showed that the second, third and fourth trial were more consistent than the first, probably due to habituation or learning. There was no difference between the second, third and fourth trial, two trials may be sufficient in testing. We also introduced 3 additional read-outs: Longest duration on the rod (s), Maximal distance covered (cm), and Number of falls to better evaluate the motor capacity over the 5 min of testing. We then used this 4-parameter analysis to capture the motor deficits of mice with mild to moderate traumatic brain injuries (by a weight dropping on the skull (Marmarou model)). We found that normalization of data to individual baseline performance was needed to reduce individual differences, and 4 trials were more sensitive than two to show motor deficits. The parameter of Maximal distance was the best in detecting statistically significant long-term motor deficits. These results show that by making adjustments to the protocol and employing a more refined analysis, it is possible to expand a widely used routine behavioral test with additional accessible parameters that detect relevant deficits in a model of mild to moderate traumatic brain injury. The modified Rotarod test maybe a valuable tool for better preclinical evaluations of drugs and therapies.
Sections du résumé
BACKGROUND
The Rotarod test with commercial apparatus is widely used to assess locomotor performance, balance and motor learning as well as the deficits resulting from diverse neurological disorders in laboratory rodents due to its simplicity and objectivity. Traditionally, the test ends when rodents drop from the accelerating, turning rod, and the only parameter used commonly is "latency to fall". The values of individual animals can often vary greatly.
RESULTS
In the present study, we established a procedure for mice with 4 consecutive days of training with 4 trials per day and modified the testing procedure by placing the mice back on the rod repeatedly after each fall until the trial ends (5 min). Data from the fourth training day as baseline results showed that the second, third and fourth trial were more consistent than the first, probably due to habituation or learning. There was no difference between the second, third and fourth trial, two trials may be sufficient in testing. We also introduced 3 additional read-outs: Longest duration on the rod (s), Maximal distance covered (cm), and Number of falls to better evaluate the motor capacity over the 5 min of testing. We then used this 4-parameter analysis to capture the motor deficits of mice with mild to moderate traumatic brain injuries (by a weight dropping on the skull (Marmarou model)). We found that normalization of data to individual baseline performance was needed to reduce individual differences, and 4 trials were more sensitive than two to show motor deficits. The parameter of Maximal distance was the best in detecting statistically significant long-term motor deficits.
CONCLUSIONS
These results show that by making adjustments to the protocol and employing a more refined analysis, it is possible to expand a widely used routine behavioral test with additional accessible parameters that detect relevant deficits in a model of mild to moderate traumatic brain injury. The modified Rotarod test maybe a valuable tool for better preclinical evaluations of drugs and therapies.
Identifiants
pubmed: 37592249
doi: 10.1186/s12915-023-01679-y
pii: 10.1186/s12915-023-01679-y
pmc: PMC10433596
doi:
Banques de données
figshare
['10.6084/m9.figshare.23899353']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
177Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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