Investigating complex I deficiency in Purkinje cells and synapses in patients with mitochondrial disease

Neuropathology and Applied Neurobiology
Alexia ChrysostomouNichola Z Lax

Abstract

Cerebellar ataxia is common in patients with mitochondrial disease, and despite previous neuropathological investigations demonstrating vulnerability of the olivocerebellar pathway in patients with mitochondrial disease, the exact neurodegenerative mechanisms are still not clear. We use quantitative quadruple immunofluorescence to enable precise quantification of mitochondrial respiratory chain protein expression in Purkinje cell bodies and their synaptic terminals in the dentate nucleus. We investigated NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 protein expression in 12 clinically and genetically defined patients with mitochondrial disease and ataxia and 10 age-matched controls. Molecular genetic analysis was performed to determine heteroplasmy levels of mutated mitochondrial DNA in Purkinje cell bodies and inhibitory synapses. Our data reveal that complex I deficiency is present in both Purkinje cell bodies and their inhibitory synapses which surround dentate nucleus neurons. Inhibitory synapses are fewer and enlarged in patients which could represent a compensatory mechanism. Mitochondrial DNA heteroplasmy demonstrated similarly high levels of mutated mitochondrial DNA in cell bodies and synapses. This is ...Continue Reading

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Citations

Jun 12, 2016·Neuropathology and Applied Neurobiology·N Z LaxD M Turnbull
Aug 14, 2020·Neural Regeneration Research·Mariana ToricelliTania Araujo Viel
Nov 3, 2016·The Journal of Pathology·Charlotte L AlstonRobert W Taylor
Feb 17, 2019·Nature Communications·Örjan PerssonMaria Falkenberg
Sep 19, 2020·Genome Biology·Scott A LujanWilliam C Copeland
Aug 28, 2018·The Journal of Pathology·Tianhong SuLaura C Greaves
Jul 24, 2021·Frontiers in Molecular Biosciences·Thomas PaßDavid Pla-Martín
Dec 17, 2020·ACS Chemical Neuroscience·Jiajia ZhaoHaitao Sun
May 22, 2017·Neurochemistry International·Tatsuya YamadaHiromi Sesaki

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Methods Mentioned

BETA
Fluorescence
PCR

Software Mentioned

Pyromark Q24
sas
Volocity®
Minitab®

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