Marked disparity between age-related changes in dopamine and other presynaptic dopaminergic markers in human striatum.
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.
Haycock
John W
JW
Department of Biochemistry and Molecular Biology, Louisiana State University Health Science Center, New Orleans 70119, USA. jhayco@lsuhsc.edu
Becker
Laurence
L
Ang
Lee
L
Furukawa
Yoshiaki
Y
Hornykiewicz
Oleh
O
Kish
Stephen J
SJ
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003342:Corpus Striatum / Q000737:chemistry*; D004298:Dopamine / Q000032:analysis*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006719:Homovanillic Acid / Q000032:analysis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D026901:Membrane Transport Proteins / Q000032:analysis; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D010751:Phosphopyruvate Hydratase / Q000032:analysis; D017729:Presynaptic Terminals / Q000737:chemistry* / Q000378:metabolism; D012016:Reference Values; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D015415:Biomarkers; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C493452:SLC18A2 protein, human; C493214:SLC6A3 protein, human; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D010751:Phosphopyruvate Hydratase; D004298:Dopamine; D006719:Homovanillic Acid