Mitotic brain cells are just as prone to mitochondrial deletions as neurons: a large-scale single-cell PCR study of the human caudate nucleus.
Mitochondria are considered a key element in the process of organismic aging, because of their fundamental role in cellular energy generation. In the course of oxidative phosphorylation, harmful free radicals are continuously produced damaging the mitochondrial (mt) genome. One of the consequences is the occurrence of large-scale deletions in mtDNA molecules. The 4977 bp common deletion accumulates exponentially with age, in a mosaic pattern, especially in postmitotic tissues. In order to investigate whether certain cell characteristics underlie this pattern of distribution, and to look for possible age-related changes, two cell types in the caudate nucleus of the human brain from five young and five senescent subjects were analysed by single-cell PCR.MAP2-positive neurons and GFAP-positive astrocytes were isolated by micromanipulation. For each of the 10 cases, at least 30 cells of each type were collected and subjected to PCR individually. Screening for the presence of the common deletion yielded no significant differences in relative distribution, neither between astrocytes and neurons, nor between healthy young and old humans. Our results imply that the age-dependent increase of the common deletion cannot come about by an increase of independent deletion events in a greater proportion of cells, and that mitotic rate is not a major cellular risk factor for deletion accumulation in the caudate nucleus.
Storm
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Department of Legal Medicine, Medical University of Luebeck, Kahlhorststrasse 31-35, 23562 Luebeck, Germany.
Rath
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Mohamed
S A
SA
Bruse
P
P
Kowald
A
A
Oehmichen
M
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Meissner
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C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D001253:Astrocytes / Q000502:physiology; D002421:Caudate Nucleus / Q000166:cytology*; D002423:Cause of Death; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008846:Micromanipulation / Q000379:methods; D008938:Mitosis / Q000235:genetics*; D009474:Neurons / Q000502:physiology; D016133:Polymerase Chain Reaction / Q000379:methods
D004272:DNA, Mitochondrial