Osorio-Paz Ixchel, Ramírez-Pérez Gabriela, Hernández-Ramírez Jesús E, Uribe-Carvajal Salvador, Salceda Rocío
División de Neurociencias, Departamento de Neurodesarrollo y Fisiología, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510, Ciudad de México, D.F., Mexico.
División de Investigación Básica, Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510, Ciudad de México, D.F., Mexico.
Mol Biol Rep. 2018 Oct;45(5):871-879. doi: 10.1007/s11033-018-4233-5. Epub 2018 Jul 7.
Diabetes affects a variety of tissues including the central nervous system; moreover, some evidence indicates that memory and learning processes are disrupted. Also, oxidative stress triggers alterations in different tissues including the brain. Recent studies indicate mitochondria dysfunction is a pivotal factor for neuron damage. Therefore, we studied mitochondrial activity in three brain regions at early type I-diabetes induction. Isolated mitochondria from normal hippocampus, cortex and cerebellum revealed different rates of oxygen consumption, but similar respiratory controls. Oxygen consumption in basal state 4 significantly increased in the mitochondria from all three brain regions from diabetic rats. No relevant differences were observed in the activity of respiratory complexes, but hippocampal mitochondrial membrane potential was reduced. However, ATP content, mitochondrial cytochrome c, and protein levels of β-tubulin III, synaptophysin, and glutamine synthase were similar in brain regions from normal and diabetic rats. In addition, no differences in total glutathione levels were observed between normal and diabetic rat brain regions. Our results indicated that different regions of the brain have specific metabolic responses. The changes in mitochondrial activity we observed at early diabetes induction did not appear to cause metabolic alterations, but they might appear at later stages. Longer-term streptozotocin treatment studies must be done to elucidate the impact of hyperglycemia in brain metabolism and the function of specific brain regions.
糖尿病会影响包括中枢神经系统在内的多种组织；此外，一些证据表明记忆和学习过程会受到干扰。另外，氧化应激会引发包括大脑在内的不同组织的改变。最近的研究表明线粒体功能障碍是神经元损伤的关键因素。因此，我们在I型糖尿病诱导早期研究了三个脑区的线粒体活性。从正常海马体、皮质和小脑中分离出的线粒体显示出不同的氧消耗率，但呼吸控制相似。糖尿病大鼠所有三个脑区的线粒体在基础状态4下的氧消耗显著增加。呼吸复合体的活性未观察到相关差异，但海马体线粒体膜电位降低。然而，正常和糖尿病大鼠脑区的ATP含量、线粒体细胞色素c以及β-微管蛋白III、突触素和谷氨酰胺合成酶的蛋白水平相似。此外，正常和糖尿病大鼠脑区之间的总谷胱甘肽水平未观察到差异。我们的结果表明大脑的不同区域有特定的代谢反应。我们在糖尿病诱导早期观察到的线粒体活性变化似乎并未引起代谢改变，但可能在后期出现。必须进行长期链脲佐菌素治疗研究，以阐明高血糖对脑代谢和特定脑区功能的影响。
