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Changes in somatodendritic but not terminal dopamine
regulation in aged rhesus monkeys
Author(s) -
Gerhardt Greg A.,
Cass Wayne A.,
Yi Ai,
Zhang Zhiming,
Gash Don M.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.0022-3042.2001.00684.x
Subject(s) - homovanillic acid , dopamine , substantia nigra , putamen , endocrinology , medicine , 3,4 dihydroxyphenylacetic acid , tyrosine hydroxylase , microdialysis , basal ganglia , parkinson's disease , senescence , biology , central nervous system , dopaminergic , serotonin , disease , receptor
For these studies, young (8–9 years), middle‐aged (14–17 years) and aged (23–28 years) rhesus monkeys were used as a model of normal aging in humans to investigate changes in dopamine (DA)‐containing neurons in senescence. Aged monkeys exhibited significant age‐related motoric declines as compared to the young animals. In vivo microdialysis studies showed that basal levels of the DA metabolites, homovanillic acid (HVA) and 3,4‐dihydroxyphenylacetic acid (DOPAC) were diminished by 44% and 79%, respectively, in␣the substantia nigra (SN) of aged monkeys. In addition, d ‐amphetamine‐evoked overflow of DA in the SN was diminished by 30% in the middle‐aged animals and 67% in the aged monkeys. Post‐mortem measures of DA and DA metabolites showed significant decreases in DA (20%), DOPAC (47%) and HVA (22%) levels in the putamen and a 25% decline in HVA tissue levels in the SN of the aged monkeys as compared to the young animals. Unbiased stereological cell counting of tyrosine hydroxylase (TH)‐immunoreactive neurons in the SN showed a small (15–20%) but significant age‐related decline in TH‐positive neurons. In addition, there was a small (15–20%) but significant decline in TH‐positive fiber density and TH‐positive cell size. In comparison to the massive loss of DA neurons responsible for the movement dysfunctions seen in Parkinson's disease, pronounced functional changes in DA release in the SN and putamen may significantly contribute to the motoric dysfunctions characterizing normal aging in rhesus monkeys.