CD200 attenuates methamphetamine-induced microglial activation and dopamine depletion
CD200 attenuates methamphetamine-induced microglial activation and dopamine depletion
复制标题
DOI：
10.1007/s11596-012-0072-0
复制
发表时间：
2012-06
期刊：
影响因子：
--
通讯作者：
Xia Yue;Dongfang Qiao;Aifeng Wang;Xiaohui Tan;Yan-hong Li;Chao Liu;Hui-jun Wang
中科院分区：
文献类型：
--
作者：
Xia Yue;Dongfang Qiao;Aifeng Wang;Xiaohui Tan;Yan-hong Li;Chao Liu;Hui-jun Wang
本研究探讨了分化分子簇200（CD200）对甲基苯丙胺（METH）诱导的神经毒性的神经保护作用。在体外实验中，分别用METH（20 μ mol/L）、METH（20 μ mol/L）+CD200-Fc（10 μ g/mL）或CD200-Fc（10 μ g/mL）处理神经元-小胶质细胞培养物。未处理的作为对照。通过流式细胞术评估以MHC-II/CD11b的比率表示的小胶质细胞活化。采用酶联免疫吸附试验（ELISA）检测活化后小胶质细胞分泌的细胞因子（IL-1 β、TNF-α）。在体内实验中，40只SD大鼠随机分为对照组、METH组、METH + CD200-Fc组和CD200-Fc组。大鼠腹腔注射METH METH组（15 mg/kg，8次，间隔12 h），（以与METH组相同的剂量和时间给药）和CD200-Fc（注射METH后第0、2、4天1mg/kg），用CD200-Fc（与METH + CD200-Fc组同时注射1mg/kg）或用生理盐水溶液在对照组中注射。采用高效液相色谱法（HPLC）测定大鼠纹状体多巴胺（DA）水平。免疫组织化学检测小胶质细胞Iba-1的表达，Iba-1是小胶质细胞活化的标志物。结果表明，METH可增加神经元-小胶质细胞培养中小胶质细胞的活化，并增加IL-1 β和TNF-α的分泌，CD200-Fc可减弱METH的这种作用。此外，CD200-Fc可部分逆转METH诱导的纹状体DA耗竭，并减少活化的小胶质细胞，即Iba-1阳性细胞的数量。结论：CD200可能通过抑制小胶质细胞活化和逆转纹状体DA耗竭对MET诱导的神经毒性具有神经保护作用。
This study examined the neuroprotective effect of cluster of differentiation molecule 200 (CD200) against methamphetamine (METH)-induced neurotoxicity. In thein vitroexperiment, neuron-microglia cultures were treated with METH (20 μmol/L), METH (20 μmol/L)+CD200-Fc (10 μg/mL) or CD200-Fc (10 μg/mL). Those untreated served as control. Microglia activation expressed as the ratio of MHC-II/CD11b was assessed by flow cytometry. The cytokines (IL-1β, TNF-α) secreted by activated microglia were detected by enzyme-linked immunosorbent assay (ELISA). In thein vivoexperiment, 40 SD rats were divided into control, METH, METH+CD200-Fc and CD200-Fc groups at random. Rats were intraperitoneally injected with METH (15 mg/kg 8 times at 12 h interval) in METH group, with METH (administered as the same dose and time as the METH group) and CD200-Fc (1 mg/kg at day 0, 2, 4 after METH injection) in METH+CD200-Fc group, with CD200-Fc (1 mg/kg injected as the same time as the METH+CD200-Fc group) or with physiological saline solution in the control group. The level of striatal dopamine (DA) in rats was measured by high-performance liquid chromatography (HPLC). The microglial cells were immunohistochemically detected for the expression of Iba-1, a marker for microglial activation. The results showed that METH could increase the microglia activation in the neuron-microglia cultures and elevate the secretion of IL-1β and TNF-α, which could be attenuated by CD200-Fc. Moreover, CD200-Fc could partially reverse the striatal DA depletion induced by METH and reduce the number of activated microglia, i.e. Iba-1-positive cells. It was concluded that CD200 may have neuroprotective effects against METH-induced neurotoxicity by inhibiting microglial activation and reversing DA depletion in striatum.