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Variability of mitochondrial energy balance across brain regions
Journal of Neurochemistry ( IF 4.7 ) Pub Date : 2020-11-15 , DOI: 10.1111/jnc.15239
XinPing Cheng 1, 2 , Andrey Y Vinokurov 3 , Evgeniy A Zherebtsov 3, 4 , Olga A Stelmashchuk 3 , Plamena R Angelova 1 , Noemi Esteras 1 , Andrey Y Abramov 1, 3
Affiliation  

Brain is not homogenous and neurons from various brain regions are known to have different vulnerabilities to mitochondrial mutations and mitochondrial toxins. However, it is not clear if this vulnerability is connected to different energy metabolism in specific brain regions. Here, using live-cell imaging, we compared mitochondrial membrane potential and nicotinamide adenine dinucleotide (NADH) redox balance in acute rat brain slices in different brain regions and further detailed the mitochondrial metabolism in primary neurons and astrocytes from rat cortex, midbrain and cerebellum. We have found that mitochondrial membrane potential is higher in brain slices from the hippocampus and brain stem. In primary co-cultures, mitochondrial membrane potential in astrocytes was lower than in neurons, whereas in midbrain cells it was higher than in cortex and cerebellum. The rate of NADH production and mitochondrial NADH pool were highest in acute slices from midbrain and midbrain primary neurons and astrocytes. Although the level of adenosine tri phosphate (ATP) was similar among primary neurons and astrocytes from cortex, midbrain and cerebellum, the rate of ATP consumption was highest in midbrain cells that lead to faster neuronal and astrocytic collapse in response to inhibitors of ATP production. Thus, midbrain neurons and astrocytes have a higher metabolic rate and ATP consumption that makes them more vulnerable to energy deprivation.

中文翻译:

大脑各区域线粒体能量平衡的变异性

脑不是同质的,已知来自各个大脑区域的神经元对线粒体突变和线粒体毒素具有不同的脆弱性。但是,尚不清楚此漏洞是否与特定大脑区域的不同能量代谢有关。在这里,我们使用活细胞成像技术比较了不同大脑区域的急性大鼠脑切片中的线粒体膜电位和烟酰胺腺嘌呤二核苷酸(NADH)氧化还原平衡,并进一步详述了来自大鼠皮层,中脑和小脑的初级神经元和星形胶质细胞的线粒体代谢。我们已经发现,海马和脑干的脑切片中线粒体膜电位更高。在原代共培养中,星形胶质细胞的线粒体膜电位低于神经元,而在中脑细胞中则高于皮质和小脑。在中脑和中脑原代神经元和星形胶质细胞的急性切片中,NADH产生的速率和线粒体NADH库最高。尽管皮层,中脑和小脑的初级神经元和星形胶质细胞中三磷酸腺苷(ATP)的水平相似,但中脑细胞中ATP的消耗率最高,这会响应ATP的产生而导致更快的神经元和星形胶质细胞崩溃。因此,中脑神经元和星形胶质细胞具有较高的代谢率和ATP消耗,这使它们更容易遭受能量剥夺。尽管皮层,中脑和小脑的初级神经元和星形胶质细胞中三磷酸腺苷(ATP)的水平相似,但中脑细胞中ATP的消耗率最高,这会响应ATP的产生而导致更快的神经元和星形胶质细胞崩溃。因此,中脑神经元和星形胶质细胞具有较高的代谢率和ATP消耗,这使它们更容易遭受能量剥夺。尽管皮层,中脑和小脑的初级神经元和星形胶质细胞中三磷酸腺苷(ATP)的水平相似,但中脑细胞中ATP的消耗率最高,这会响应ATP的产生而导致更快的神经元和星形胶质细胞崩溃。因此,中脑神经元和星形胶质细胞具有较高的代谢率和ATP消耗,这使它们更容易遭受能量剥夺。
更新日期:2020-11-15
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