Institute of Functional Biology and Genomics, University of Salamanca, CSIC, 37007, Salamanca, Spain; Centro de Investigación Biomédica en Red Sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain; Institute of Biomedical Research of Salamanca, University Hospital of Salamanca, University of Salamanca, CSIC, 37007, Salamanca, Spain.
Institute of Functional Biology and Genomics, University of Salamanca, CSIC, 37007, Salamanca, Spain.
Redox Biol. 2021 May;41:101917. doi: 10.1016/j.redox.2021.101917. Epub 2021 Mar 3.
Cells naturally produce mitochondrial reactive oxygen species (mROS), but the in vivo pathophysiological significance has long remained controversial. Within the brain, astrocyte-derived mROS physiologically regulate behaviour and are produced at one order of magnitude faster than in neurons. However, whether neuronal mROS abundance differentially impacts on behaviour is unknown. To address this, we engineered genetically modified mice to down modulate mROS levels in neurons in vivo. Whilst no alterations in motor coordination were observed by down modulating mROS in neurons under healthy conditions, it prevented the motor discoordination caused by the pro-oxidant neurotoxin, 3-nitropropionic acid (3-NP). In contrast, abrogation of mROS in astrocytes showed no beneficial effect against the 3-NP insult. These data indicate that the impact of modifying mROS production on mouse behaviour critically depends on the specific cell-type where they are generated.
细胞自然会产生线粒体活性氧（mROS），但其在体内的病理生理意义长期以来一直存在争议。在大脑中，星形胶质细胞衍生的 mROS 生理性地调节行为，其产生速度比神经元快一个数量级。然而，神经元 mROS 的丰度是否会对行为产生不同的影响尚不清楚。为了解决这个问题，我们通过基因工程改造了小鼠，使其体内神经元中的 mROS 水平降低。尽管在健康条件下降低神经元中的 mROS 水平不会改变运动协调能力，但它可以防止促氧化神经毒素 3-硝基丙酸（3-NP）引起的运动不协调。相比之下，星形胶质细胞中 mROS 的消除对 3-NP 的损伤没有有益的影响。这些数据表明，改变 mROS 产生对小鼠行为的影响取决于产生 mROS 的特定细胞类型。
