Cass Wayne A, Peters Laura E
Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY, USA.
Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY, USA.
Neurochem Int. 2017 Sep;108:222-229. doi: 10.1016/j.neuint.2017.04.001. Epub 2017 Apr 5.
Parkinson's disease (PD) is a progressive and debilitating neurodegenerative disorder that affects over one million people in the United States. Previous studies, carried out in young adult rats, have shown that calcitriol, the active metabolite of vitamin D, can be neuroprotective in 6-hydroxydopamine (6-OHDA) models of PD. However, as PD usually affects older individuals, the ability of calcitriol to promote dopaminergic recovery was examined in lesioned young adult (4 month old), middle-aged (14 month old) and aged (22 month old) rats. Animals were given a single injection of 12 μg 6-OHDA into the right striatum. Four weeks later they were administered vehicle or calcitriol (1.0 μg/kg, s.c.) once a day for eight consecutive days. In vivo microdialysis experiments were carried out three weeks after the calcitriol or vehicle treatments to measure potassium and amphetamine evoked overflow of DA from both the left and right striata. In control animals treated with 6-OHDA and vehicle there were significant reductions in evoked overflow of DA on the lesioned side of the brain compared to the contralateral side. The calcitriol treatments significantly increased evoked overflow of DA from the lesioned striatum in both the young adult and middle-aged rats. However, the calcitriol treatments did not significantly augment DA overflow in the aged rats. Postmortem tissue levels of striatal DA were also increased in the young and middle-aged animals, but not in the aged animals. In the substantia nigra, the calcitriol treatments led to increased levels of DA in all three age groups. Thus, the effects of calcitriol were similar in the young adult and middle-aged animals, but in the aged animals the effects of calcitriol were diminished. These results suggest that calcitriol may help promote recovery of dopaminergic functioning in injured nigrostriatal neurons; however, the effectiveness of calcitriol may be reduced in aging.
帕金森病（PD）是一种进行性且使人衰弱的神经退行性疾病，在美国影响着超过100万人。此前在年轻成年大鼠身上进行的研究表明，维生素D的活性代谢物骨化三醇在帕金森病的6-羟基多巴胺（6-OHDA）模型中具有神经保护作用。然而，由于帕金森病通常影响老年人，因此研究了骨化三醇促进多巴胺能恢复的能力，实验对象为损伤的年轻成年（4个月大）、中年（14个月大）和老年（22个月大）大鼠。给动物右侧纹状体单次注射12μg 6-OHDA。四周后，它们连续八天每天接受溶剂或骨化三醇（1.0μg/kg，皮下注射）。在骨化三醇或溶剂处理三周后进行体内微透析实验，以测量钾和苯丙胺诱发的多巴胺从左右纹状体的溢出情况。在用6-OHDA和溶剂处理的对照动物中，与对侧相比，脑损伤侧诱发的多巴胺溢出显著减少。骨化三醇处理显著增加了年轻成年和中年大鼠损伤纹状体中诱发的多巴胺溢出。然而，骨化三醇处理并未显著增加老年大鼠的多巴胺溢出。年轻和中年动物死后纹状体多巴胺的组织水平也有所增加，但老年动物没有。在黑质中，骨化三醇处理导致所有三个年龄组的多巴胺水平升高。因此，骨化三醇在年轻成年和中年动物中的作用相似，但在老年动物中骨化三醇的作用减弱。这些结果表明，骨化三醇可能有助于促进受损黑质纹状体神经元中多巴胺能功能的恢复；然而，骨化三醇的有效性在衰老过程中可能会降低。
