食蟹猴年龄相关的运动功能减退及其与纹状体多巴胺转运体的关系

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

目的研究食蟹猴老化过程中运动行为和脑内纹状体多巴胺系统功能变化及两者之间的相关关系。方法选取4岁、10岁和15岁3个年龄组的健康食蟹猴共29只,利用计算机化的网络摄像头视频检测系统和行为分析软件连续采集和分析每个动物8h随意运动活动总量,各年龄组分别选取4只动物用多巴胺转运体(DAT)配体99mTc-TRODAT-1结合单光子发射体层摄影术(SPECT)显像观察脑内纹状体多巴胺转运体放射性摄取率的变化。结果在4岁、10岁和15岁年龄组,8h随意运动活动总量(×106)分别为5·00±1·93,3·28±1·02,2·79±0·67,在10岁和15岁较之4随年龄组分别降低了34·50%和55·71%(P<0·05,P<0·01),但此两个年龄组运动活动总量无显著差异(P>0·05);纹状体99mTc-TRODAT-1放射性摄取率分别为2·98±0·08,2·56±0·12和2·27±0·35,10岁和15岁较之4随年龄组分别降低了14·00%和25·60%,但仅4岁与15岁年龄组存在显著相关关系(P<0·01)。二者均随着年龄的增长呈逐渐减低的趋势,直线回归分析显示两者分别与年龄呈负相关关系(r=-0·57,P=0·001;r=-0·86,P<0·01)。8h随意运动活动总量与纹状体99mTc-TRODAT-1放射性摄取率呈显著的正相关关系(r=0·70,P<0·05)。结论正常食蟹猴老化过程中,脑内多巴胺神经系统功能的减退伴随着运动行为的减少,两者之间的相关关系进一步佐证了运动功能的减退可能是由于纹状体内多巴胺神经元功能减退所致。

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 99m^Tc-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 respectivel4. 00% and 25.60% decrease in the uptake rate of 99m^Tc-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.