Effect of aging on lazabemide binding, monoamine oxidase activity and monoamine metabolites in human frontal cortex.
Age-related modifications of monoamine oxidase-A and -B (MAO-A and MAO-B) and amine metabolite concentrations were studied in human frontal cortex taken postmortem from 22 subjects of various ages (21-75 years). Qualitative and quantitative analysis for MAO-B was provided by kinetic studies with a specific radioligand, [3H]lazabemide. The data demonstrated a significant (P < 0.05) positive correlation between the density of [3H]lazabemide binding sites (Bmax) and age of the subject, without showing an apparent modification in the dissociation constant (KD) of the radioligand. In parallel experiments, MAO-B but not MAO-A activity was shown to correlate with age (P < 0.05). The concentrations of the amine metabolites 4-hydroxy-3-methoxyphenylacetic acid (HVA), 5-hydroxyindole-3-acetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), 4-hydroxy-3-methoxyphenylglycol (MHPG) and 3,4-dihydroxyphenylglycol (DHPG) were all devoid of a correlation with age. Neither did the concentrations of these metabolites relate to the respective subject's MAO-B enzymatic activity nor to [3H]lazabemide Bmax. A correlation, though rather weak, was obtained between MAO-A activity and MHPG concentration (P = 0.045). The MAO-A and -B enzyme characteristics in subjects who had committed suicide (n = 9) did not differ from those of subjects deceased for other causes (n = 13). Among the measured monoamine metabolites the concentrations of DOPAC and HVA were higher in the suicide versus control group (P < 0.05). The present data confirm in a direct manner that the increase in MAO-B activity in aging brain is due to an enhancement of the number of active sites of the enzyme and not through modifications of its kinetic characteristics. Furthermore, that neither the characteristics nor the activity of the enzyme are changed in the frontal cortex of suicide victims compared to control subjects.
Galva
M D
MD
Department of Pharmacology, Chemotherapy and Toxicology, University of Milan, Italy.
Bondiolotti
G P
GP
Olasmaa
M
M
Picotti
G B
GB
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D015306:Biogenic Monoamines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism*; D010848:Picolinic Acids / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000201:enzymology / Q000378:metabolism*; D013405:Suicide
D015306:Biogenic Monoamines; D008996:Monoamine Oxidase Inhibitors; D010848:Picolinic Acids; C059303:lazabemide; D008995:Monoamine Oxidase