Increased Mitochondrial DNA Deletions in Substantia Nigra Dopamine Neurons of the Aged Rat
Gemma M. Parkinson,
Christopher V. Dayas,
Doug W. Smith.
The dopaminergic neurons of the substantia nigra (SN), which constitute the origin of the nigrostriatal
system, are vulnerable to age-related degenerative processes. For example, in humans there is a relatively
small age-related loss of neurons but a marked decline of the dopaminergic phenotype associated with
impaired voluntary motor control. However, the mechanisms responsible for the dysfunction and degeneration
of SN dopamine neurons remain poorly understood. One potential contributor is mitochondrial dysfunction,
resulting from an increased abundance of mitochondrial DNA (mtDNA) mutations such as deletions. Human studies
have identified relatively high levels of mtDNA deletions in these cells in both aging and Parkinson’s disease (>35%),
with a higher abundance of deletions (>60%) in individual neurons with mitochondrial dysfunction. However, it is unknown
whether similar mtDNA mutations occur in other species such as the rat. In the present study, we quantified
mtDNA deletion abundance in laser microdissected SN dopaminergic neurons from young and old F344 rats. Our results
indicate that mtDNA deletions accumulated with age, with approximately 20% more mtDNA deletions in SN dopaminergic
neurons from old compared to young animals. Thus, while rat SN dopaminergic neurons do accumulate mtDNA deletions
with aging, this does not reflect the deletion burden in humans, and other mechanisms may be operating to compensate
for age-related mtDNA damage in the rat SN dopaminergic neurons.
Keywords: Aging, dopamine neuron, mitochondrial DNA deletions, rat, substantia nigra.
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