Early behavioral deficits in R6/2 mice suitable for use in preclinical drug testing.

Area of Science:

• Neuroscience
• Genetics
• Pharmacology

Background:

• Huntington's disease (HD) is a neurodegenerative disorder.
• It is caused by an expanded glutamine repeat in the huntingtin gene.
• Understanding molecular effects is key for developing new treatments.

Purpose of the Study:

• To identify early behavioral deficits in a mouse model of HD.
• To assess the suitability of automated behavioral tests for high-throughput drug screening.
• To establish reliable markers for disease progression in early stages.

Main Methods:

• Utilized a mouse model of Huntington's disease (R6/2 transgenics).
• Employed automated behavioral tests, including running wheel activity and climbing behavior.
• Compared behavioral data with rotarod performance and grip strength at different ages.

Main Results:

• Reduced running wheel activity and climbing behavior were observed in R6/2 mice as early as 4.5 weeks.
• These deficits occurred before changes in rotarod performance or grip strength.
• Power calculations indicated the running wheel test's suitability for early-stage, high-throughput drug screening.

Conclusions:

• Early, automated behavioral tests can detect motor function deficits in HD mouse models.
• The running wheel test is a cost-effective and efficient method for early drug screening in HD.
• These findings correlate with early synaptic dysfunction in the striatum of young HD mice.