Aging and the nigrostriatal dopamine system: a non-human primate study.
The present study examined neurochemical, morphological and functional markers of the nigrostriatal dopamine system in young, intermediate-aged and old squirrel monkeys. Striking reductions in motoric activity were observed with advancing age. significant age-related loss of dopamine occurred in the substantia nigra (70%) and the putamen (30%) but not in the caudate. There was a strong correlation between the reductions in motoric activity and the loss of putamen dopamine. However, nigrostriatal dopamine loss did not appear to be the consequence of age-related loss of dopaminergic nigral neurons since the number of tyrosine immunoreactive cells was not significantly different among the three age groups. These results suggest that the aging squirrel monkey demonstrates the age-related loss of nigrostriatal dopamine thought to occur in humans and identify this non-human primate as a useful model to further investigate the underlying mechanism(s) and functional consequences of age-related decline of the nigrostriatal dopamine system. In addition, the selective loss of dopamine in the putamen but not the caudate parallels the regional vulnerability observed in Parkinson's disease, an age-related neurodegenerative disorder, raising the possibility of a relationship between normal aging and the development of this disease. Finally, because the number of tyrosine hydroxylase (TH) positive cells remains constant with age, these results raise the possibility that therapeutic strategies aimed at increasing dopamine concentrations may benefit elderly individuals.
Irwin
I
I
Parkinson's Institute, Sunnyvale, California 94089.
DeLanney
L E
LE
McNeill
T
T
Chan
P
P
Forno
L S
LS
Murphy
G M
GM
Di Monte
D A
DA
Sandy
M S
MS
Langston
J W
JW
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D012453:Saimiri; D012701:Serotonin / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid