Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin - 682 022, Kerala, India.
J Neurol Sci. 2013 Aug 15;331(1-2):31-7. doi: 10.1016/j.jns.2013.04.020. Epub 2013 May 28.
Oxidative stress-induced neuronal cell death has been implicated in Parkinson's disease (PD). Oxidative stress initiated by 6-hydroxydopamine (6-OHDA) causes mitochondrial dysfunction leading to apoptosis and Parkinsonian neurodegeneration. We investigated the neuroprotective potential of serotonin (5-HT), gamma amino butyric acid (GABA) and autologous bone marrow cells (BMC) in combination against oxidative stress-induced cell death. PD was induced in adult male Wistar rats by intranigral infusion of 6-OHDA (8 μg/μl). The activities of antioxidant enzymes--superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were analysed. The extent of lipid peroxidation was quantified by measuring the formation of thiobarbituric acid reactive substances (TBARs). Real Time PCR gene expression of SOD, CAT and GPx were performed using specific Taqman probes. 6-OHDA induced decreased activity of SOD, CAT and GPx in corpus striatum was significantly reversed to near control (p<0.001) by treatment with 5-HT, GABA and bone marrow cells. Gene expression studies of SOD, CAT and GPx using Real Time PCR confirmed the above observation. TBAR levels were elevated (p<0.001) in 6-OHDA treated rats indicating lipid peroxidation. 5-HT and GABA along with autologous bone marrow cell supplementation significantly ameliorated 6-OHDA-induced lipid peroxidation (p<0.001). Our results suggest a new therapeutic strategy of neuroprotection against damage by oxidative stress in Parkinson's disease.
氧化应激诱导的神经元细胞死亡与帕金森病（PD）有关。6-羟多巴胺（6-OHDA）引发的氧化应激导致线粒体功能障碍，进而引发细胞凋亡和帕金森神经退行性变。我们研究了 5-羟色胺（5-HT）、γ-氨基丁酸（GABA）和自体骨髓细胞（BMC）联合应用对氧化应激诱导的细胞死亡的神经保护潜力。通过向成年雄性 Wistar 大鼠黑质内注射 6-OHDA（8μg/μl）诱导 PD。分析抗氧化酶——超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）的活性。通过测量硫代巴比妥酸反应物质（TBARs）的形成来定量脂质过氧化的程度。使用特定的 Taqman 探针进行 SOD、CAT 和 GPx 的实时 PCR 基因表达分析。6-OHDA 诱导的纹状体 SOD、CAT 和 GPx 活性降低，用 5-HT、GABA 和骨髓细胞治疗后明显恢复到接近对照水平（p<0.001）。使用实时 PCR 进行的 SOD、CAT 和 GPx 的基因表达研究证实了上述观察结果。6-OHDA 处理的大鼠 TBAR 水平升高（p<0.001），表明脂质过氧化。5-HT 和 GABA 以及自体骨髓细胞补充显著改善了 6-OHDA 诱导的脂质过氧化（p<0.001）。我们的结果表明了一种新的治疗策略，即通过抗氧化应激来对抗帕金森病的损伤。
