Marked disparity between age-related changes in dopamine and other pre-synaptic dopaminergic markers in striatum

Department of Biochemistry and Molecular Biology, Louisiana State University Health Science Center, New Orleans 70119, USA.
Journal of Neurochemistry (Impact Factor: 4.24). 12/2003; 87(3):574-85. DOI: 10.1046/j.1471-4159.2003.02017.x
Source: PubMed

ABSTRACT Because age-related changes in brain dopaminergic innervation are assumed to influence human disorders involving dopamine (DA), we measured the levels of several presynpatic DAergic markers [DA, homovanillic acid, tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AADC), vesicular monoamine transporter 2 (VMAT2), and dopamine transporter (DAT)] in post-mortem human striatum (caudate and putamen) from 56 neurologically normal subjects aged 1 day to 103 years. Striatal DA levels exhibited pronounced (2- to 3-fold) post-natal increases through adolescence and then decreases during aging. Similarly, TH and AADC increased almost 100% during the first 2 post-natal years; however, the levels of TH and, to a lesser extent, AADC then declined to adult levels by approximately 30 years of age. Although VMAT2 and DAT levels closely paralleled those of TH, resulting in relatively constant TH to transporter ratios during development and aging, a modest but significant decline (13%) in DAT levels was observed in only caudate during aging. This biphasic post-natal pattern of the presynaptic markers suggests that striatal DAergic innervation/neuropil appears to continue to develop well past birth but appears to become overelaborated and undergo regressive remodeling during adolescence. However, during adulthood, a striking discrepancy was observed between the loss of DA and the relative preservation of proteins involved in its biosynthesis and compartmentation. This suggests that declines in DA-related function during adulthood and senescence may be explained by losses in DA per se as opposed to DAergic neuropil.

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Available from: Yoshiaki Furukawa, Oct 13, 2014
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    • "Therefore, comparisons of dopamine functions across the lifespan have, so far, based on results from animal studies (e.g., Tarazi and Baldessarini, 2000; see Herlenius and Lagercrantz, 2004 for review) or from human post-mortem studies (e.g., Haycock et al., 2003; Tunbridge et al., 2007). For instance, postnatally dopamine level in the striatum increases 2–3 folds through adolescence and then decreases during aging (Haycock et al., 2003). Consider also the evidence from another study (Tunbridge et al., 2007), which shows that the activity of an enzyme that regulates extracellular dopamine levels in the prefrontal cortex (i.e., the catechol-o-methyltransferase enzyme) increases about 2-folds from neonate to adulthood, and decline slightly afterwards. "
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