Inhibition of thrombin-induced microglial activation and NADPH oxidase by minocycline protects dopaminergic neurons in the substantia nigra in vivo
Inhibition of thrombin-induced microglial activation and NADPH oxidase by minocycline protects dopaminergic neurons in the substantia nigra in vivo
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DOI：
10.1111/j.1471-4159.2005.03503.x
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发表时间：
2005-12-01
影响因子：
4.7
通讯作者：
Jin, BK
中科院分区：
文献类型：
--
作者：
Choi, SH;Lee, DY;Jin, BK
目前的研究表明，小胶质细胞NADPH氧化酶的激活和活性氧（ROS）的产生与凝血酶诱导的黑质多巴胺能神经元在体内的变性。在大鼠黑质（SN）注射凝血酶后7天，酪氨酸羟化酶免疫细胞化学显示黑质多巴胺能神经元的显着损失。这种细胞死亡伴随着本地化的末端脱氧核苷酸转移酶介导的荧光素UTP缺口末端标记（TUNEL）染色多巴胺能神经元内。这种神经毒性被半合成四环素衍生物米诺环素拮抗，观察到的神经保护作用与米诺环素抑制NADPH氧化酶衍生的ROS产生和促炎细胞因子表达的能力相关，包括白细胞介素-1 β和诱导型一氧化氮合酶，来自活化的小胶质细胞。这些结果表明，小胶质细胞NADPH氧化酶可能是一个可行的目标，对氧化损伤的神经保护。
The present study shows that activation of microglial NADPH oxidase and production of reactive oxygen species (ROS) is associated with thrombin-induced degeneration of nigral dopaminergic neurons in vivo. Seven days after thrombin injection in the rat substantia nigra (SN), tyrosine hydroxylase immunocytochemistry showed a significant loss of nigral dopaminergic neurons. This cell death was accompanied by localization of terminal deoxynucleotidyl transferase-mediated fluorecein UTP nick-end labelling (TUNEL) staining within dopaminergic neurons. This neurotoxicity was antagonized by the semisynthetic tetracycline derivative, minocycline, and the observed neuroprotective effects were associated with the ability of minocycline to suppress NADPH oxidase-derived ROS production and pro-inflammatory cytokine expression, including interleukin-1 beta and inducible nitric oxide synthase, from activated microglia. These results suggest that microglial NADPH oxidase may be a viable target for neuroprotection against oxidative damage.