Vitamin D3 attenuates 6-hydroxydopamine-induced neurotoxicity in rats

Jia Yi Wang, Jian Nan Wu, Tao Lin Cherng, Barry J. Hoffer, Hsiu Hui Chen, Cesario V. Borlongan, Yun Wang

研究成果: 雜誌貢獻文章同行評審

211 引文 斯高帕斯(Scopus)


Previous reports have demonstrated that exogeneous administration of glial cell line-derived neurotrophic factor (GDNF) reduces ventral mesencephalic (VM) dopaminergic (DA) neuron damage induced by 6-hydroxydopamine (6-OHDA) lesioning in rats. Recent studies have shown that 1,25-dihydroxyvitamin D3 (D3) enhances endogenous GDNF expression in vitro and in vivo. The purpose of present study was to investigate if administration of D3 in vivo and in vitro would protect against 6-OHDA-induced DA neuron injury. Adult male Sprague-Dawley rats were injected daily with D3 or with saline for 8 days and then lesioned unilaterally with 6-OHDA into the medial forebrain bundle. Locomotor activity was measured using automated activity chambers. We found that unilateral 6-OHDA lesioning reduced locomotor activity in saline-pretreated animals. Pretreatment with D3 for 8 days significantly restored locomotor activity in the lesioned animals. All animals were sacrificed for neurochemical analysis 6 weeks after lesioning. We found that 6-OHDA administration significantly reduced dopamine (DA), 3,4-dihydroxy-phenylacetic acid (DOPAC) and homovanilic acid (HVA) levels in the substantia nigra (SN) on the lesioned side in the saline-treated rats. D3 pretreatment protected against 6-OHDA-mediated depletion of DA and its metabolites in SN. Using primary cultures obtained from the VM of rat embryos, we found that 6-OHDA or H2O2 alone caused significant cell death. Pretreatment with D3 (10-10 M) protected VM neurons against 6-OHDA- or H2O2-induced cell death in vitro. Taken together, our data indicate that D3 pretreatment attenuates the hypokinesia and DA neuronal toxicity induced by 6-OHDA. Since both H2O2 and 6-OHDA may injure cells via free radical and reactive oxygen species, the neuroprotection seen here may operate via a reversal of such a toxic mechanism.
頁(從 - 到)67-75
期刊Brain Research
出版狀態已發佈 - 6月 15 2001

ASJC Scopus subject areas

  • 神經病學(臨床)
  • 分子生物學
  • 一般神經科學
  • 發展生物學


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