ABSTRACT
Objective To investigate the behavioral characteristics of circadian rhythm disturbance in 3xTg-AD mice.Methods The free-running period,average activity per hour,total amount of exercise and circadian amplitude were examined with voluntary wheel-running test in 3-to 9-month-old C57BL/6 and 3xTg-AD mice under 12 h light/12 h dark cycle and constant darkness environment.Results In constant darkness environment,the free-running period in 3-month-old 3xTg-AD mice was (23.2±0.4) h,and shorter than the period((23.5±0.2) h) in C57BL/6 mice.In 6-and 9-month-old 3xTg-AD mice,activity pattern was disorganized,without clear boundary between activity and rest phase.The free-running period was unavailable.The circadian amplitude and total exercise amount were(40.6± 11.5) counts/5 min and(2.6±0.1) × 104 counts/d,(37.0±20.8) counts/5 min and(2.3±0.4) × 104 counts/d,(29.3± 11.0) counts/5 min and(1.6± 0.9) × 104 counts/d in 3-,6-and 9-month-old 3xTg-AD mice,respectively,which was significantly lower than that in age-matched C57BL/6 mice.In 12 h light/12 h dark cycle,the circadian amplitude and total exercise amount of 3-,6-and 9-month-old 3xTg-AD mice were (87.0 ± 37.8) counts/5 min and (2.2 ± 0.8) × 104 counts/d,(25.9± 6.3) counts/5 min and (1.1 ± 0.2) × 104 counts/d,(14.3 ± 5.7) counts/5 min and (0.6 ± 0.3)× 104 counts/d respectively,and with a significant decrease from the age of 6 months.Meanwhile,the locomotor activity decreased at night and increased during the day.Conclusion The endogenous circadian rhythm disturbance emerges in 3xTg-AD mice at 3-month-old,while the exogenous circadian rhythm disorder appears at 6-month-old;the degree of disorder in circadian rhythm is gradually aggravated with the increase of age in of the AD mice.