Smith Michael P, Fletcher-Turner Anita, Yurek David M, Cass Wayne A
Department of Anatomy and Neurobiology, MN-225 Chandler Medical Center, University of Kentucky, Lexington, 40536-0298, USA.
Neurochem Res. 2006 Apr;31(4):533-9. doi: 10.1007/s11064-006-9048-4.
Calcitriol has been implicated as an agent that has neuroprotective effects in various animal models of diseases, possibly by upregulating glial cell line-derived neurotrophic factor (GDNF). The present study examined the neuroprotective effects of calcitriol in a model of early Parkinson's disease. Rats were treated daily with calcitriol or saline for 7 days before an intraventricular injection of 6-hydroxydopamine (6-OHDA), and then for 1 day or daily for 3(1/2) to 4 weeks after lesioning. Evoked overflow and tissue content of dopamine (DA) were determined 3(1/2) to 4 weeks post lesion. The 8-day calcitriol treatment did not attenuate 6-OHDA-induced decreases in evoked overflow of DA, nor did it protect against 6-OHDA-induced reductions in tissue levels of DA in the striatum or substantia nigra. However, the long-term calcitriol treatment did significantly increase evoked overflow of DA, as well as the amount of DA in the striatum, compared to saline treated animals. GDNF was significantly increased in the substantia nigra, but not in the striatum, of non-lesioned, calcitriol treated rats. These results suggest that long-term treatment with calcitriol can provide partial protection for dopaminergic neurons against the effects of intraventricularly administered 6-OHDA.
骨化三醇被认为是一种在各种疾病动物模型中具有神经保护作用的药物，可能是通过上调胶质细胞源性神经营养因子（GDNF）来实现的。本研究检测了骨化三醇在早期帕金森病模型中的神经保护作用。在脑室内注射6-羟基多巴胺（6-OHDA）前7天，大鼠每天接受骨化三醇或生理盐水治疗，损伤后再分别接受1天或持续3.5至4周的每日治疗。在损伤后3.5至4周测定多巴胺（DA）的诱发溢出量和组织含量。8天的骨化三醇治疗并未减弱6-OHDA诱导的DA诱发溢出量的减少，也未防止6-OHDA诱导的纹状体或黑质中DA组织水平的降低。然而，与生理盐水处理的动物相比，长期骨化三醇治疗确实显著增加了DA诱发溢出量以及纹状体中DA的含量。在未损伤的、接受骨化三醇治疗的大鼠中，黑质中的GDNF显著增加，但纹状体中未增加。这些结果表明，长期使用骨化三醇治疗可为多巴胺能神经元提供部分保护，使其免受脑室内注射6-OHDA的影响。
