Pasbakhsh Parichehr, Omidi Negar, Mehrannia Kobra, Sobhani Ali Gholi, Ragerdi Kashani Iraj, Abbasi Mehdi, Kord Valeshabad Ali
Dept. of Anatomy, School of Medicine, University of Tehran, Tehran, Iran.
Iran Biomed J. 2008 Oct;12(4):217-22.
Free radical formation and oxidative stress might play an important role in the pathogenesis of Parkinson's disease (PD). In vitro data indicate that neuromelanin (NM) pigment is formed the excess cytosolic catecholamine that is not accumulated into synaptic vesicles via the vesicular monoamine transporter 2 (VMAT2). We designed this study to investigate the neuroprotective effects of vitamin E in the early model of PD.
Male rats (n = 40) with unbiased rotational behavior were randomly divided into five groups: sham operated group (SH, n = 8), vehicle-treated SH group (SH + V, n = 8), vitamin E-treated SH group (SH + E, n = 8), vehicle-treated lesion group (L + V, n = 8) and vitamin E-treated lesion group (L + E, n = 8). Unilateral intrastriatal 6-hydroxydopamine (12.5 microl) lesioned rats were treated intramuscularly with alpha-tocopherol acid succinate (24 I.U/kg, intramuscular [i.m.]) 1 h before surgery and three times per week for 2 month post-surgery. To evaluate the vitamin E pretreatment efficacy, tyrosine hydroxylase (TH) immunoreactivity and immunostaining intensity (ISI) for monoamine transporter 2 were used.
TH immunohistochemical analyses showed a reduction of 20 percent in locus coeruleus (LC) cell number of vitamin E pretreated lesioned group but the cell number dropped to 60 percent in the lesioned group. The ISI of the cells was measured for VMAT2 in LC. Lesioned groups: 1) had the lowest VMAT2 ISI of all neurons; 2) There was an inverse relationship between VMAT2 ISI and NM pigment in the locus and 3) Neurons with the highest VMAT2 ISI also had high TH ISI.
The data support the hypothesis that repeated i.m. administration of vitamin E exerts a protective effect on the LC neurons in the early model of PD.
自由基形成和氧化应激可能在帕金森病（PD）的发病机制中起重要作用。体外数据表明，神经黑色素（NM）色素是由未通过囊泡单胺转运体2（VMAT2）积累到突触小泡中的过量胞质儿茶酚胺形成的。我们设计本研究以探讨维生素E在早期PD模型中的神经保护作用。
将具有无偏旋转行为的雄性大鼠（n = 40）随机分为五组：假手术组（SH，n = 8）、溶剂处理的SH组（SH + V，n = 8）、维生素E处理的SH组（SH + E，n = 8）、溶剂处理的损伤组（L + V，n = 8）和维生素E处理的损伤组（L + E，n = 8）。单侧纹状体内注射6-羟基多巴胺（12.5微升）损伤的大鼠在手术前1小时肌肉注射α-生育酚琥珀酸酯（24国际单位/千克，肌肉注射[i.m.]），并在手术后每周三次，持续2个月。为评估维生素E预处理效果，使用酪氨酸羟化酶（TH）免疫反应性和单胺转运体2的免疫染色强度（ISI）。
TH免疫组织化学分析显示，维生素E预处理损伤组的蓝斑（LC）细胞数量减少了20%，但损伤组的细胞数量降至60%。测量了LC中VMAT2的细胞ISI。损伤组：1）所有神经元中VMAT2的ISI最低；2）LC中VMAT2的ISI与NM色素之间呈负相关；3）VMAT2的ISI最高的神经元TH的ISI也高。
数据支持以下假设，即重复肌肉注射维生素E对早期PD模型中的LC神经元具有保护作用。
