Changes in somatodendritic but not terminal dopamine regulation in aged rhesus monkeys
Changes in somatodendritic but not terminal dopamine regulation in aged rhesus monkeys
复制标题
DOI：
10.1046/j.0022-3042.2001.00684.x
复制
发表时间：
2002-01-01
影响因子：
4.7
通讯作者：
Gash, DM
中科院分区：
文献类型：
--
作者：
Gerhardt, GA;Cass, WA;Gash, DM
在这些研究中，年轻（8 - 9岁）、中年（14 - 17岁）和老年（23 - 28岁）的恒河猴被用作人类正常衰老的模型，以研究衰老过程中含多巴胺（DA）神经元的变化。与年轻动物相比，老年猴表现出明显的与年龄相关的运动能力下降。体内微透析研究表明，老年猴黑质中DA代谢产物高香草酸（HVA）和3,4 - 二羟基苯乙酸（DOPAC）的基础水平分别降低了44%和79%。此外，中年动物中D - 安非他明诱发的黑质DA溢出减少了30%，老年猴中减少了67%。对死后的DA和DA代谢产物的检测显示，与年轻动物相比，老年猴的壳核中DA（20%）、DOPAC（47%）和HVA（22%）水平显著降低，黑质中HVA组织水平下降了25%。对黑质中酪氨酸羟化酶（TH）免疫反应性神经元进行无偏立体细胞计数显示，TH阳性神经元有少量（15 - 20%）但显著的与年龄相关的减少。此外，TH阳性纤维密度和TH阳性细胞大小也有少量（15 - 20%）但显著的下降。与帕金森病中导致运动功能障碍的大量DA神经元缺失相比，黑质和壳核中DA释放的显著功能变化可能对恒河猴正常衰老的运动功能障碍有重要影响。
For these studies, young (8-9 years), middle-aged (14-17 years) and aged (23-28 years) rhesus monkeys were used as a model of normal aging in humans to investigate changes in dopamine (DA)-containing neurons in senescence. Aged monkeys exhibited significant age-related motoric declines as compared to the young animals. In vivo microdialysis studies showed that basal levels of the DA metabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were diminished by 44% and 79%, respectively, in the substantia nigra (SN) of aged monkeys. In addition, D-amphetamine-evoked overflow of DA in the SN was diminished by 30% in the middle-aged animals and 67% in the aged monkeys. Post-mortem measures of DA and DA metabolites showed significant decreases in DA (20%), DOPAC (47%) and HVA (22%) levels in the putamen and a 25% decline in HVA tissue levels in the SN of the aged monkeys as compared to the young animals. Unbiased stereological cell counting of tyrosine hydroxylase (TH)-immunoreactive neurons in the SN showed a small (15-20%) but significant age-related decline in TH-positive neurons. In addition, there was a small (15-20%) but significant decline in TH-positive fiber density and TH-positive cell size. In comparison to the massive loss of DA neurons responsible for the movement dysfunctions seen in Parkinson's disease, pronounced functional changes in DA release in the SN and putamen may significantly contribute to the motoric dysfunctions characterizing normal aging in rhesus monkeys.