Institute of Neuropathology, Bellvitge University Hospital, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de LLobregat, Catalonia, Spain.
University Hospital Donostia, San Sebastián, Spain.
Brain Pathol. 2018 Jan;28(1):43-57. doi: 10.1111/bpa.12474. Epub 2017 Mar 16.
Altered mitochondrial function is characteristic in the substantia nigra in Parkinson's disease (PD). Information about mitochondria in other brain regions such as the cerebral cortex is conflicting mainly because most studies have not contemplated the possibility of variable involvement depending on the region, stage of disease progression and clinical symptoms such as the presence or absence of dementia. RT-qPCR of 18 nuclear mRNAs encoding subunits of mitochondrial complexes and 12 mRNAs encoding energy metabolism-related enzymes; western blotting of mitochondrial proteins; and analysis of enzymatic activities of complexes I, II, II, IV and V of the respiratory chain were assessed in frontal cortex area 8 and the angular gyrus of middle-aged individuals (MA), and those with incidental PD (iPD), long-lasting PD with parkinsonism without dementia (PD) and long-lasting PD with dementia (PDD). Up-regulation of several genes was found in frontal cortex area 8 in PD when compared with MA and in the angular gyrus in iPD when compared with MA. Marked down-regulation of genes encoding mitochondrial subunits and energy metabolism-related enzymes occurs in frontal cortex but only of genes coding for energy metabolism-related enzymes in the angular gyrus in PDD. Significant decrease in the protein expression levels of several mitochondrial subunits encoded by these genes occurs in frontal cortex area 8 and angular gyrus in PDD. Moreover, expression of MT-ND1 which is encoded by mitochondrial DNA is also reduced in PDD. Reduced enzymatic activity of complex III in frontal cortex area 8 and angular gyrus is observed in PD, but dramatic reduction in the activity of complexes I, II, II and IV in both regions characterizes PDD. Dementia in the context of PD is linked to region-specific deregulation of genomic genes encoding subunits of mitochondrial complexes and to marked reduction in the activity of mitochondrial complexes I, II, III and IV.
线粒体功能改变是帕金森病（PD）中黑质的特征。关于大脑皮质等其他脑区的线粒体信息存在冲突，主要是因为大多数研究没有考虑到区域、疾病进展阶段和临床症状（如痴呆的存在与否）的不同可能导致的不同参与程度。我们评估了中年个体（MA）和偶发性帕金森病（iPD）、无痴呆的持续性帕金森病（PD）和有痴呆的持续性帕金森病（PDD）的额皮质 8 区和角回中 18 种编码线粒体复合物亚基的核 mRNA 和 12 种编码能量代谢相关酶的 mRNA 的实时定量 PCR（RT-qPCR）；线粒体蛋白的 Western blot；以及呼吸链复合物 I、II、III、IV 和 V 的酶活性分析。与 MA 相比，PD 患者额皮质 8 区的多个基因上调，与 MA 相比，iPD 患者角回的多个基因上调。PD 患者额皮质的编码线粒体亚基和能量代谢相关酶的基因明显下调，但 PDD 患者角回只有编码能量代谢相关酶的基因下调。这些基因编码的几个线粒体亚基的蛋白表达水平在 PDD 的额皮质区 8 和角回显著下降。此外，线粒体 DNA 编码的 MT-ND1 的表达在 PDD 中也减少。PD 患者额皮质区 8 和角回的复合物 III 酶活性降低，但两个区域的复合物 I、II、II 和 IV 的活性显著降低，是 PDD 的特征。PD 相关的痴呆与编码线粒体复合物亚基的基因组基因的区域特异性失调以及线粒体复合物 I、II、III 和 IV 的活性显著降低有关。
