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Age-related decline in motor behavior and its association with striatal dopamine transporter in cynomolgus monkeys

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机构: [1]100053首都医科大学北京宣武医院神经内科,神经生物学室,教育部神经变性病重点实验室 [2]广西壮族自治区桂林医学院病理科 [3]广西南宁灵康赛诺科生物科技有限公司灵康实验室 [4]100053首都医科大学北京宣武医院神经内科,神经生物学室,细胞治疗中心
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关键词: Aging Corpus striatum Hypokinesia Macaca fascicularis Membrane transport proteins Nerve tissue proteins

摘要:
Objective: To investigate the age-related alterations of motor behavior and striatal dopamine transporter (DAT) as well as their correlation in normal cynomolgus monkeys. Methods: A total of 29 healthy cynomolgus monkeys rangingfrom 3.5-15.5 years old were used. The 8-hour quantitative measurements of random movement were evaluated utilizing a computerized webcam monitoring system, moreover, in vivo striatal DAT level was determined by 99mTc-TRODAT-1 SPECT imaging. Results: It was shown that the 8-hour total counts (million) were 5.00 ± 1.93, 3.28 ± 1.02, 2.79 ± 0.67 in 4-, 10- and 15-year old groups, and a significant decrease of 34.50% and 55.71% activity counts was found in the 10- and 15-year old group compared to the 4-year old group, respectively (P < 0.05), but the difference between the latter two groups was not statistically different (P > 0.05). The average specific uptake values were 2.98 ± 0.08 (4-year age), 2.56 ± 0.12 (10-year age) and 2.27 ± 0.35 (15-year age) respectively, indicating a respective 14.00% and 25.60% decrease in the uptake rate of 99mTc-TRODAT-1 in 10- and 15-year old animals, respectively, as compared to the 4-year old animals. Comparison of inter-group (ANOVA) analysis displayed a significant difference (P < 0.05) only between 4- and 15-year old groups (P < 0.01). A significant decline in 8 hours home cage activity counts and in vivo striatal DAT uptake was found with aging, respectively (r = -0.57, P = 0.001; r = -0.86, P < 0.01). A statistical correlativity between the age-related decrease of in vivo striatal DAT uptake ratio and the decline of 8-hour activity counts were demonstrated (r = 0.70, P < 0.05). Conclusion: In normal cynomolgus monkeys, the age-related decline of striatal dopaminergic nerve terminals is associated with age-related decline of motor behavior, supporting the putative hypothesis that the decline of motor function is resulted from deterioration of nigrostriatal dopaminergic system.

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第一作者机构: [1]100053首都医科大学北京宣武医院神经内科,神经生物学室,教育部神经变性病重点实验室
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通讯机构: [1]100053首都医科大学北京宣武医院神经内科,神经生物学室,教育部神经变性病重点实验室
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