Overexpression of CB2 cannabinoid receptors results in neuroprotection against behavioral and neurochemical alterations induced by intracaudate administration of 6-hydroxydopamine
Overexpression of CB2 cannabinoid receptors results in neuroprotection against behavioral and neurochemical alterations induced by intracaudate administration of 6-hydroxydopamine
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DOI：
10.1016/j.neurobiolaging.2010.09.012
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发表时间：
2012-02-01
影响因子：
4.2
通讯作者：
Manzanares, Jorge
中科院分区：
文献类型：
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作者：
Ternianov, Alexander;Perez-Ortiz, Jose M.;Manzanares, Jorge
CB 2大麻素受体的作用，在行为和神经化学的变化所引起的6-羟基多巴胺（6-OHDA）的尾状核给药进行了评估。6-将OHDA（12 μ g/4 μ L）或其载体注射到过表达CB 2大麻素受体（CB 2xP）的小鼠和野生型（WT）小鼠的尾壳核（CPu）中。评估运动障碍、情绪行为和认知改变。通过免疫细胞化学测定CB 2xP小鼠和WT小鼠CPu和/或黑质（SN）中的酪氨酸羟化酶（TH）、胶质细胞酸性蛋白（GFAP）和离子化钙结合衔接分子1（Iba-1）。还在6-OHDA处理和假处理小鼠的CPu和皮质中测量氧化/亚硝化和神经炎症参数。6-OHDA处理的CB 2xP小鼠表现出比6-OHDA处理的WT小鼠显著更少的运动恶化。SN和CPu中酪氨酸羟化酶的免疫细胞化学分析显示，CB 2xP小鼠的病变明显少于WT小鼠。GFAP和Iba-1免疫染色显示CB 2xP小鼠中CPu治疗区域的星形胶质细胞和小胶质细胞募集较少。假处理CB 2xP小鼠的纹状体和大脑皮质中的丙二醛（MDA）浓度低于假处理WT小鼠。6-OHDA的给药增加了WT小鼠和CB 2xP小鼠中的MDA水平;与匹配的假处理对照相比，它增加了单独WT小鼠纹状体中的氧化型（GSSG）/还原型（GSH）谷胱甘肽比率。结果显示，CB 2大麻素受体的过表达降低了运动障碍和多巴胺能神经元损失的程度，减少了星形胶质细胞和小胶质细胞向病变的募集，并降低了各种氧化参数的水平。这些结果表明，CB 2受体提供对多巴胺能损伤的神经保护。(C)2012 Elsevier Inc. All rights reserved.
The role of CB2 cannabinoid receptors in the behavioral and neurochemical changes induced by intracaudate administration of 6-hydroxydopamine (6-OHDA) was evaluated. 6-OHDA (12 mu g/4 mu L) or its vehicle was injected in the caudate-putamen (CPu) of mice overexpressing the CB2 cannabinoid receptor (CB2xP) and wild type (WT) mice. Motor impairment, emotional behavior, and cognitive alterations were evaluated. Tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule 1 (Iba-1) were measured by immunocytochemistry in the CPu and/or substantia nigra (SN) of CB2xP mice and WT mice. Oxidative/nitrosative and neuroinflammatory parameters were also measured in the CPu and cortex of 6-OHDA-treated and sham-treated mice. 6-OHDA-treated CB2xP mice presented significantly less motor deterioration than 6-OHDA-treated WT mice. Immunocytochemical analysis of tyrosine hydroxylase in the SN and CPu revealed significantly fewer lesions in CB2xP mice than in WT mice. GFAP and Iba-1 immunostaining revealed less astrocyte and microglia recruitment to the treated area of the CPu in CB2xP mice. Malonyldialdehyde (MDA) concentrations were lower in the striatum and cerebral cortex of sham-treated CB2xP mice than in sham-treated WT mice. The administration of 6-OHDA increased MDA levels in both WT mice and CB2xP mice; it increased the oxidized (GSSG)/reduced (GSH) glutathione ratio in the striatum in WT mice alone compared with matched sham-treated controls. The results revealed that overexpression of CB2 cannabinoid receptors decreased the extent of motor impairment and dopaminergic neuronal loss, reduced the recruitment of astrocytes and microglia to the lesion, and decreased the level of various oxidative parameters. These results suggest that CB2 receptors offer neuroprotection against dopaminergic injury. (C) 2012 Elsevier Inc. All rights reserved.