Decreased alpha-synuclein expression in the aging mouse substantia nigra.
Because of its normal function in synaptic plasticity and pathologic involvement in age-related neurodegenerative diseases, the protein alpha-synuclein could play an important role in aging processes. Here we compared alpha-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 alpha-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 alpha-synuclein protein; immunoreactivity of midbrain sections stained with an anti-alpha-synuclein antibody was most robust in 2-month-old mice and weakest in 20-month-old animals. Lowering of nigral alpha-synuclein could not be explained by a loss of dopaminergic neurons and was relatively specific since no change in beta-synuclein mRNA and protein occurred with advancing age. Finally, age-related decreases in alpha-synuclein were widespread throughout the mouse brain, affecting other regions (e.g., hippocampus) besides the substantia nigra. The data suggest that loss of alpha-synuclein could contribute to or be a marker of synaptic dysfunction in the aging brain. They also emphasize important differences in alpha-synuclein expression between rodents and primates since earlier reports have shown a marked elevation of alpha-synuclein protein in the substantia nigra of older humans and non-human primates.
Mak
Sally K
SK
The Parkinson's Institute, 675 Almanor Avenue, Sunnyvale, CA 94085, USA.
McCormack
Alison L
AL
Langston
J William
JW
Kordower
Jeffrey H
JH
Di Monte
Donato A
DA
D000375:Aging / Q000378:metabolism*; D000818:Animals; D004298:Dopamine / Q000502:physiology; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013378:Substantia Nigra / Q000254:growth & development* / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051844:alpha-Synuclein / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D051844:alpha-Synuclein; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine