Marked disparity between age-related changes in dopamine and other presynaptic dopaminergic markers in human striatum.

AbstractBecause age-related changes in brain dopaminergic inner-vation are assumed to influence human disorders involvingdopamine (DA), we measured the levels of several presyn-patic DAergic markers [DA, homovanillic acid, tyrosinehydroxylase (TH), aromatic L -amino acid decarboxylase(AADC), vesicular monoamine transporter 2 (VMAT2), anddopamine transporter (DAT)] in post-mortem human striatum(caudate and putamen) from 56 neurologically normal sub-jects aged 1 day to 103 years. Striatal DA levels exhibitedpronounced (2- to 3-fold) post-natal increases through adol-escence and then decreases during aging. Similarly, TH andAADC increased almost 100% during the first 2 post-natalyears; however, the levels of TH and, to a lesser extent, AADCthen declined to adult levels by approximately 30 years of age.Although VMAT2 and DAT levels closely paralleled those ofTH, resulting in relatively constant TH to transporter ratiosduring development and aging, a modest but significantdecline (13%) in DAT levels was observed in only caudateduring aging. This biphasic post-natal pattern of the presy-naptic markers suggests that striatal DAergic innervation/neuropil appears to continue to develop well past birth butappears to become overelaborated and undergo regressiveremodeling during adolescence. However, during adulthood, astriking discrepancy was observed between the loss of DAand the relative preservation of proteins involved in its bio-synthesis and compartmentation. This suggests that declinesin DA-related function during adulthood and senescence maybe explained by losses in DA per se as opposed to DAergicneuropil.Keywords: aromatic