Age-related changes in the N-methyl-D-aspartate receptor binding sites within the human basal ganglia.
The present study examined the regional differences in dopamine transporter binding sites and NMDA receptor complex binding based on autoradiographic images obtained in postmortem sections of human normal brain tissues. In middle-aged control tissues, high and comparable levels of [(3)H]CFT binding were observed in the caudate nucleus, putamen, and accumbens nucleus without significant alteration along the rostrocaudal axis and ventral and dorsal parts of these nuclei. In aging normal brain tissues, dopamine binding sites for [(3)H]CFT were significantly reduced in the caudate nucleus, putamen, and accumbens nucleus. l-[(3)H]Glutamate, [(3)H]MK-801, and [(3)H]glycine binding to the NMDA receptor complex was lower in aging brain tissues than in middle-aged controls. Significant correlation did occur between age and [(3)H]CFT binding and between age and l-[(3)H]glutamate, [(3)H]MK-801, and [(3)H]glycine binding sites. These results demonstrate that the basal ganglia have age-associated reductions in dopamine transporter uptake and NMDA receptors. These data support hypoactive activity of the NMDA receptor complex system with advancing age. The dopamine transporter uptake and NMDA receptors appear to be vulnerable to the aging process in the basal ganglia.
Villares
J C
JC
Aging and Neurodegenerative Diseases Brain Bank Investigation Laboratory, Universidade Federal de São Paulo, São Paulo, 04023-062, Brazil. Villares@Psicobio.epm.br
Stavale
J N
JN
D000328:Adult; D000368:Aged; D000375:Aging; D001345:Autoradiography; D001479:Basal Ganglia / Q000254:growth & development* / Q000378:metabolism*; D002421:Caudate Nucleus / Q000254:growth & development / Q000378:metabolism; D002423:Cause of Death; D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009714:Nucleus Accumbens / Q000254:growth & development / Q000378:metabolism; D011699:Putamen / Q000254:growth & development / Q000378:metabolism; D011869:Radioligand Assay; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D018765:Dopamine Uptake Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D016291:Dizocilpine Maleate; D003042:Cocaine