Araújo G W, Beyer C, Arnold S
Institute for Neuroanatomy, Faculty of Medicine, RWTH, Aachen, Germany.
J Neuroendocrinol. 2008 Jul;20(7):930-41. doi: 10.1111/j.1365-2826.2008.01747.x. Epub 2008 Apr 28.
The regulation of mitochondrial energy metabolism plays an essential role in the central nervous system (CNS). Abnormalities of the mitochondrial respiratory chain often accompany neurodegenerative diseases. This makes mitochondria a perfect target for strategies of cellular protection against toxic compounds and pathological conditions. Steroid hormones, such as oestrogen, are well-known to fulfil a protective role in the brain during ischaemic and degenerative processes. Because astrocytes function as the major energy supplier in the CNS, we have analysed oestrogen effects on the mitochondrial respiratory chain of this cell type. In our studies, we applied semi- and quantitative polymerase chain reaction analysis of gene expression and polarographic measurements of the respiratory chain activity of mitochondria. We observed that structural and functional properties were regulated dependent on the oestrogen exposure time and the brain region, but independent of the nuclear oestrogen receptors. We could demonstrate that long-term oestrogen exposure increases the subunit gene expression of respiratory chain complexes and the mitochondrial DNA content, thereby indicating an up-regulation of the amount of mitochondria per cell together with an increase of mitochondrial energy production. This could represent an important indirect mechanism by which long-term oestrogen exposure protects neurones from cell death under neurotoxic conditions. On the other hand, we observed short-term effects of oestrogen on the activity of mitochondrial, proton-pumping respiratory chain complexes. In astrocytes from the cortex, respiratory chain activity was decreased, whereas it was increased in astrocytes from the mesencephalon. An increased production of reactive oxygen species would be the consequence of an increased respiratory chain activity in mesencephalic astrocytes. This could explain the different efficiencies of oestrogen-mediated short-term protection in distinct brain regions, but also indicates the limitations for a therapeutic short-term application of oestrogen.
线粒体能量代谢的调节在中枢神经系统（CNS）中起着至关重要的作用。线粒体呼吸链异常常伴随神经退行性疾病。这使得线粒体成为针对有毒化合物和病理状况的细胞保护策略的理想靶点。众所周知，类固醇激素，如雌激素，在缺血和退行性过程中对大脑发挥保护作用。由于星形胶质细胞是中枢神经系统中的主要能量供应者，我们分析了雌激素对这种细胞类型线粒体呼吸链的影响。在我们的研究中，我们应用了基因表达的半定量和定量聚合酶链反应分析以及线粒体呼吸链活性的极谱测量。我们观察到，结构和功能特性的调节取决于雌激素暴露时间和脑区，但与核雌激素受体无关。我们能够证明，长期雌激素暴露会增加呼吸链复合物的亚基基因表达和线粒体DNA含量，从而表明每个细胞中线粒体数量的上调以及线粒体能量产生的增加。这可能代表了一种重要的间接机制，通过该机制长期雌激素暴露可在神经毒性条件下保护神经元免于细胞死亡。另一方面，我们观察到雌激素对线粒体质子泵呼吸链复合物活性的短期影响。在来自皮质的星形胶质细胞中，呼吸链活性降低，而在来自中脑的星形胶质细胞中则升高。中脑星形胶质细胞呼吸链活性增加的结果将是活性氧产生增加。这可以解释雌激素介导的短期保护在不同脑区的不同效率，但也表明了雌激素短期治疗应用的局限性。
