title: Single-cell analysis of mtDNA deletion levels in sporadic amyotrophic lateral sclerosis.
abstract: One possible cause for the neuronal loss in sporadic amyotrophic lateral sclerosis (S-ALS) is an increase of free radicals, which may produce oxidative damage to susceptible biomolecules, which, in turn, can damage the mitochondrial DNA (mtDNA). Following laser microdissection of single motor neurons from paraffin-embedded autopsy tissue, we analyzed the presence of a common mtDNA deletion, the 5 kb common deletion (CD). Spinal cord neurons showed slightly higher CD detection rate in patients than controls (94% vs 75%). No significant differences were found between patients and controls for neurons derived from other motor or non-motor regions. A PCR assay of serial DNA dilutions (10-fold) showed no CD level differences between motor neurons in S-ALS and controls. These data suggest that neuronal death in S-ALS is not associated with significant accumulation of mtDNA deletions.
authors.affiliation: Department of Neuropathology, Otto-von-Guericke-University, Leipziger Strasse 44, D-39120 Magdeburg, Germany. Christian.Marwin@Medizin.Uni-Magdeburg.de
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.forename: Elmar
authors.initials: E
authors.lastname: Kirches
authors.forename: Guido
authors.initials: G
authors.lastname: Krause
authors.forename: Falk R
authors.initials: FR
authors.lastname: Wiedemann
authors.forename: Christian K
authors.initials: CK
authors.lastname: Vorwerk
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bogerts
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Schildhaus
authors.forename: Knut
authors.initials: K
authors.lastname: Dietzmann
authors.forename: Regine
authors.initials: R
authors.lastname: Schneider-Stock
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D042282:Microdissection / Q000379:methods; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D017382:Reactive Oxygen Species / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species