Laboratory of Cellular Neurobiology, Department of Physiology and Biophysics, Institute of Biomedical Sciences, USP, SP, Brazil.
Neuroscience. 2010 Nov 10;170(4):1249-60. doi: 10.1016/j.neuroscience.2010.07.065. Epub 2010 Aug 20.
Redox processes associated with controlled generation of reactive oxygen species (ROS) by NADPH oxidase (Nox) add an essential level of regulation to signaling pathways underlying physiological processes. We evaluated the ROS generation in the main visual relays of the mammalian brain, namely the superior colliculus (SC) and the dorsal lateral geniculate nucleus (DLG), after ocular enucleation in adult rats. Dihydroethidium (DHE) oxidation revealed increased ROS generation in SC and DLG between 1 and 30 days postlesion. ROS generation was decreased by the Nox inhibitors diphenyleneiodonium chloride (DPI) and apocynin. Real-time PCR results revealed that Nox 2 was upregulated in both retinorecipient structures after deafferentation, whereas Nox 1 and Nox 4 were upregulated only in the SC. To evaluate the role of ROS in structural remodeling after the lesions, apocynin was given to enucleated rats and immunohistochemistry was conducted for markers of neuronal remodeling into SC and DLG. Immunohistochemical data showed that ocular enucleation produces an increase of neurofilament and microtubule-associated protein-2 immunostaining in both SC and DLG, which was markedly attenuated by apocynin treatment. Taken together, the findings of the present study suggest a novel role for Nox-induced ROS signaling in mediating neuronal remodeling in visual areas after ocular enucleation.
NADPH 氧化酶（Nox）通过氧化还原过程来控制活性氧物质（ROS）的生成，从而为生理过程的信号通路提供了重要的调节作用。我们评估了成年大鼠眼球摘除后，其大脑主要视觉中继中的 ROS 生成情况，包括上丘（SC）和外侧膝状体核（DLG）。二氢乙啶（DHE）氧化显示，损伤后 1 至 30 天 SC 和 DLG 中的 ROS 生成增加。Nox 抑制剂二苯基碘（DPI）和 apocynin 降低了 ROS 的生成。实时 PCR 结果显示，去传入后，两种视网膜接受结构中 Nox 2 上调，而 Nox 1 和 Nox 4 仅在上丘上调。为了评估 ROS 在损伤后结构重塑中的作用，将 apocynin 给予眼球摘除大鼠，并对 SC 和 DLG 中的神经元重塑标志物进行免疫组织化学染色。免疫组织化学数据显示，眼球摘除导致 SC 和 DLG 中的神经丝和微管相关蛋白-2 免疫染色增加，而 apocynin 处理显著减弱了这种增加。总之，本研究的结果表明，Nox 诱导的 ROS 信号在介导眼球摘除后视觉区域神经元重塑中具有新的作用。
