Aims: 

Nucleosides are well known neuromodulators that have a wide range of physiological and pathophysiological roles in the human brain. For example, adenosine, inosine, guanosine and uridine participate in the mechanisms of cognition, memory, sleep and pain, as well as epilepsy, Alzheimer's disease, Huntington's disease and Parkinson's disease. For better understanding function of nucleosides in the central nervous system, to reveal distribution of nucleoside levels and changes of nucleoside concentrations by age and gender are actual requirements.

Methods: 

Nucleoside levels of post mortem samples (n=1015) from 61 human brain and 4 spinal cord areas were measured by HPLC. Using back-extrapolation coefficients (a multiplying factor for calculating concentrations of investigated substances for the living state) we established in vivo tissue levels of four nucleosides (uridine, inosine, guanosine and adenosine) and three of their metabolites (uracil, hypoxanthine and xanthine).

Results: 

Average concentrations of the brain samples (regardless to their anatomical locations, gender or age; mean±S.E.M.) were the following (pmol/mg wet tissue weight): adenosine 8.5±0.58, inosine 74.8±2.84, guanosine 13.2±0.62, uridine 35.1±1.26, uracil 7.1±0.36, hypoxanthine 58.3±1.58 and xanthine 35.1±1.17. Concentration of nucleosides were uneven in the human central nervous system and highest in the temporal cortex, the vestibular and cochlear nuclei, the amygdala, and the caudate nucleus, whereas lowest in the zona incerta, the habenula, the substantia nigra, and the locus coeruleus. We revealed that concentrations of inosine, guanosine, adenosine and uridine in the frontal cortex and the cerebral white matter are age- and gender-dependent.

Conclusion: 

Our findings suggest that the roles of nucleosides may be different in functionally different human brain areas and the nucleoside microenvironment could be an important factor in aging process in the brain.