title: Mitochondrial activity in the frontal cortex area 8 and angular gyrus in Parkinson's disease and Parkinson's disease with dementia.
abstract: 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.
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de LLobregat, Catalonia, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Garcia-Esparcia
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de LLobregat, Catalonia, Spain.
authors.forename: Anusha
authors.initials: A
authors.lastname: Koneti
authors.affiliation: University Hospital Donostia, San Sebastián, Spain.|Ikerbasque (Basque Foundation for Science), Bilbao, Spain.|Biodonostia Research Institute, San Sebastián, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: M Cruz
authors.initials: MC
authors.lastname: Rodríguez-Oroz
authors.affiliation: Biodonostia Research Institute, San Sebastián, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Belen
authors.initials: B
authors.lastname: Gago
authors.affiliation: Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.|Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Department of Cell Biology, University of Barcelona, Barcelona, Spain.|Institute of Neurosciences, University of Barcelona, Barcelona, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Del Rio
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de LLobregat, Catalonia, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.|Institute of Neurosciences, University of Barcelona, Barcelona, Spain.|Department of Pathology and Experimental Therapeutics, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003704:Dementia / Q000209:etiology / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000378:metabolism; D010296:Parietal Lobe / Q000378:metabolism*; D010300:Parkinson Disease / Q000150:complications / Q000378:metabolism* / Q000628:therapy; D012333:RNA, Messenger / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C497604:SNCA protein, human; D051844:alpha-Synuclein
keywords: PDD; Parkinson disease; cerebral cortex; dementia; energy metabolism; incidental PD; mitochondria; oxidative phosphorylation; respiratory chain