Age‐Correlated Loss of Dopaminergic Binding Sites in Human Basal Ganglia

Abstract

Human caudate nucleus, putamen, substantia nigra, and nucleus accumbens were analyzed for the effects of age on dopaminergic binding sites. Decreases in the number of dopaminergic binding sites were detected with age in caudate nucleus (44 specimens from three sample groups) and substantia nigra (n = 12). In caudate nucleus, the decline in [3H]2-amino-6, 7-dehydroxy-1, 2, 3, 4-tetrahydronaphthalene sites was three times greater than for [3H]spiperone, but age changes were significant in only two of the three sampling groups. No age changes in binding were detected in the putamen (n = 44) or nucleus accumbens. Age, sex, and tissue source all significantly contributed to variance. However, cause of death, time from death to tissue freezing, and length of storage did not influence dopaminergic binding in the caudate nucleus or putamen. Relative to the life-span, the age-correlated decrease in dopaminergic binding sites of human brain approximates that in aging rodent striatum. Comparisons of altered dopaminergic binding with other age-correlated changes suggest that neuronal loss may not be involved in the loss of binding sites before midlife.

In Vivo Imaging of Cerebral Dopamine D3 Receptors in Alcoholism

“…This is in accordance with existing in vitro and in vivo evidence of a significant decline in DRD2/3 density with age (Antonini et al, 1993;Ichise et al, 1998;Ishibashi et al, 2009;Rinne et al, 1990;Severson et al, 1982;Volkow et al, 1998;Wong et al, 1997). In addition, among our ADP, DRD3 blockade in the putamen and thalamus was negatively associated with age.…”

“…To explore whether PET outcome measures and other variables, such as drinking parameters, smoking parameters, and psychometric data, were related, multiple linear regression analysis with V T or D DRD3 V T (%) was included as the dependent variable. Age was also included as a covariate in these analyses as DRD2/3 levels decline with age (Antonini et al, 1993;Ichise et al, 1998;Ishibashi et al, 2009;Rinne et al, 1990;Severson et al, 1982;Volkow et al, 1998;Wong et al, 1997). To assess whether there was a significant V T blockade in the cerebellum, onetailed paired t-test for pre-vs post-blockade cerebellar V T values for each group was applied.…”

The ageing brain: normal and abnormal memory

“…In addition, there is an age-related decrease in dopaminergic binding sites in the caudate nucleus (Severson et al 1982) and the substantia nigra and a loss of neurons in the substantia nigra of about 6% per year (McGeer et al 1977). This loss of dopamine is thought to be responsible for many neurological symptoms that increase in frequency with age, such as decreased armswing and increased rigidity (Odenheimer et al 1994).…”

Primate aging in the mammalian scheme: the puzzle of extreme variation in brain aging

“…2). Synapse loss progressing across middle-age was first described by Finch and colleagues for dopaminergic D2 binding sites in rodents (Severson and Finch 1980) and in humans (Severson et al 1982;Morgan et al 1987), where it approximates a loss of 0.5-1.0%/year in humans and comparable percent for rodents when normalized per unit adult lifespan. The same synapse loss rate was verified for a large set of normal human brains in immunocytochemically identified synaptophysin (SYN) by Robert Terry and Bob Katzman's group (Masliah et al 1993).…”

“…a Dopamine D2 receptors in postmortem striatum mouse, determined as Bmax by Scatchard analysis (Severson and Finch 1980). b Human D2 sites (Severson et al 1982). c Synaptophysin immunoreactive presynaptic terminals (SYN-IR) in human cerebral cortex (Masliah et al 1993).…”