Decreased Alpha-Synuclein Expression in the Aging Mouse Substantia Nigra


Mak, S. K., McCormack, A. L., Langston, J. W., Kordower, J. H., & Di Monte, D. A. (2009). Decreased α-synuclein expression in the aging mouse substantia nigra. Experimental neurology, 220(2), 359-365.


Because of its normal function in synaptic plasticity and pathologic involvement in age-related neurodegenerative diseases, the protein α-synuclein could play an important role in aging processes. Here we compared α-synuclein expression in the substantia nigra and other brain regions of young (2-month-old), middle-aged (10-month-old), and old (20-month-old) mice. Levels of nigral α-synuclein mRNA, as assessed by both in situ hybridization and qPCR, were high in young mice and progressively declined in middle-aged and old animals. This age-dependent mRNA loss was paralleled by a marked reduction of α-synuclein protein; immunoreactivity of midbrain sections stained with an anti-α-synuclein antibody was most robust in 2-month-old mice and weakest in 20-month-old animals. Lowering of nigral α-synuclein could not be explained by a loss of dopaminergic neurons and was relatively specific since no change in β-synuclein mRNA and protein occurred with advancing age. Finally, age-related decreases in α-synuclein were widespread throughout the mouse brain, affecting other regions (e.g., hippocampus) besides the substantia nigra. The data suggest that loss of α-synuclein could contribute to or be a marker of synaptic dysfunction in the aging brain. They also emphasize important differences in α-synuclein expression between rodents and primates since earlier reports have shown a marked elevation of α-synuclein protein in the substantia nigra of older humans and non-human primates.

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