Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
Brain Res. 2010 Mar 10;1319:44-53. doi: 10.1016/j.brainres.2010.01.017. Epub 2010 Jan 14.
Male rats (21days) were assigned to enriched environment (EE) or to standard environment (SE) for 1year. Oxygen consumption and the sensitivity to calcium induced mitochondrial permeability transition (MPT), through mitochondrial membrane potential (DeltaPsi(m)) and swelling, were determined in isolated hippocampal and cerebral cortex mitochondria. Mitochondrial H(2)O(2) production rate, and NOS activity and expression associated with mitochondrial membranes were also assayed. Results showed that state 3 respiratory rate was increased by 80% in cerebral cortex mitochondria from EE rats and no changes were observed in hippocampal mitochondria after EE exposure. Calcium induced-swelling was 40% and 53% lower in hippocampal and cerebral cortex mitochondria from EE rats, as compared with SE rats. Calcium loading induced membrane depolarization in cerebral cortex mitochondria from EE rats but did not affect mitochondrial DeltaPsi(m) in hippocampal mitochondria from EE animals, probably due to decreased H(2)O(2) formation. NO production associated to mitochondrial membranes was increased by 195% in cerebral cortex mitochondria but decreased by 47% in hippocampal mitochondria from EE rats, as compared with SE rats. Western blot analysis from nNOS protein expression associated to mitochondrial samples revealed a similar pattern. Our results suggest that in hippocampus and cerebral cortex, EE exposure protects mitochondria against calcium-induced MPT maintaining a convenient membrane potential, which assures a continuous energy supply.
雄性大鼠(21 天)被分配到丰富环境(EE)或标准环境(SE)中,进行为期 1 年的实验。在分离的海马和大脑皮质线粒体中,测定了耗氧量以及钙诱导的线粒体通透性转换(MPT)的敏感性,通过线粒体膜电位(DeltaPsi(m))和肿胀来衡量。还测定了线粒体 H(2)O(2)产生率以及与线粒体膜相关的 NOS 活性和表达。结果表明,EE 大鼠大脑皮质线粒体的状态 3 呼吸速率增加了 80%,而 EE 暴露后海马线粒体没有变化。与 SE 大鼠相比,EE 大鼠的海马和大脑皮质线粒体的钙诱导肿胀分别降低了 40%和 53%。EE 大鼠的大脑皮质线粒体在钙加载时会发生膜去极化,但不会影响 EE 动物海马线粒体的线粒体 DeltaPsi(m),这可能是由于 H(2)O(2)形成减少所致。与 SE 大鼠相比,EE 大鼠的大脑皮质线粒体与线粒体相关的 NO 生成增加了 195%,而海马线粒体则减少了 47%。与线粒体样本相关的 nNOS 蛋白表达的 Western blot 分析显示出类似的模式。我们的结果表明,在海马体和大脑皮质中,EE 暴露可保护线粒体免受钙诱导的 MPT,从而维持方便的膜电位,确保持续的能量供应。