Gender- and age-dependent changes in nucleoside levels in the cerebral cortex and white matter of the human brain.

Nucleosides are neuromodulators that participate in various neuronal functions in the brain. In previous studies, we described regional differences in the concentrations of nucleosides and their derivatives in the human brain. To better understand the functions of nucleosides in the central nervous system, we investigated gender- and age-dependent changes in the levels of nucleosides and their metabolites. The concentrations of uridine, inosine, guanosine and adenosine as well as uracil, hypoxanthine and xanthine were measured in the frontal cortex and white matter of post-mortem brain tissue samples of middle-aged and old men as well as women. The average in vivo concentrations calculated from the 40 samples investigated (regardless of anatomical locations, gender or age; mean +/- S.E.M.) were as follows (pmol/mg wet tissue weight): 9.7 +/- 0.8 adenosine, 85.8 +/- 3.9 inosine, 14.3 +/- 0.9 guanosine, 37.3 +/- 1.8 uridine, 8.9 +/- 0.6 uracil, 63.3 +/- 2.1 hypoxanthine and 38.7 +/- 1.5 xanthine. We conclude that concentration differences between uridine, inosine, guanosine and adenosine in the frontal cortex and cerebral white matter suggest that nucleoside metabolism is altered with aging and regulated differently between men and women.