Noninvasive assessment of aromatic L-amino acid decarboxylase activity in aging rhesus monkey brain in vivo.
The effect of aging on aromatic L-amino acid decarboxylase (AAAD) activity in rhesus monkey striatum was assessed in vivo using PET imaging. Two analogs of L-DOPA, 6-fluoro-m-tyrosine (FMT) and 6-fluoro-L-DOPA (FDOPA), were used to image rhesus monkeys of various ages. Results show that when the animals were grouped between young (3-11 years) and aged (25-37 years), FDOPA uptake in the older animals showed a 21% decline (P < 0.0005), while FMT uptake in young and older animals were not different. On the other hand, when individual uptake values were plotted vs. age, linear regression analysis showed FDOPA uptake similarly declined with age (r = -0.84, P < 0.001) while FMT uptake increased with age (r = 0.66, P < 0.05). Since FMT pharmacokinetics has been shown to be unaffected by metabolic steps occurring after the AAAD step, while FDOPA traces all the steps involved in L-DOPA metabolism, FMT is a suitable tracer to assess AAAD activity while FDOPA traces dopamine turnover. Based on these tracer characteristics, this study found that AAAD activity is maintained or increased in the aging rhesus monkey striatum while the FDOPA uptake decreases with age consistent with age-related declines in neuronal mechanisms whose overall effect is increased striatal dopamine turnover and clearance. Furthermore, comparison of results of this study with previous studies support the notion that the effect of aging in the dopamine system is different from that of MPTP-induced parkinsonism.
Dejesus
O T
OT
Department of Medical Physics, University of Wisconsin Medical School Madison, Wisconsin 53706, USA. odejesus@facstaff.wisc.edu
Endres
C J
CJ
Shelton
S E
SE
Nickles
R J
RJ
Holden
J E
JE
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D008253:Macaca mulatta / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D014055:Tomography, Emission-Computed; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*
C080704:6-fluoro-3-tyrosine; C043437:fluorodopa F 18; D014443:Tyrosine; D004295:Dihydroxyphenylalanine; D001142:Aromatic-L-Amino-Acid Decarboxylases