Uneven regional distribution of nucleotide metabolism in human brain

Adenine and uridine nucleotides and adenosine are proposed to act as neuromodulators and other nucleotides and nucleosides are also suggested to be involved in brain function. A following major step towards the verification of the functional role of nucleotides and nucleosides in the brain would be the examination of regional distribution of purines, pyrimidines and the enzymes involved in their metabolism. Using our recently developed chromatography-based assay for nucleosides from tissue homogenates, we analysed nucleosides in microdissected samples derived from various regions of human brain. Marked differences in the levels of nucleosides were measured in the cerebral cortex, cerebellar cortex, thalamus and white matter. The greatest levels of most nucleosides were found in the cerebral cortex, followed by the cerebellar cortex and the white matter while the smallest concentrations were found in the thalamus, although adenosine and xanthine showed a different distribution pattern in these brain areas. Within the cerebral cortex, the measured substances showed little variations except certain high levels in the cingulate and low levels in the frontal cortex. Even distribution of nucleosides was found in the thalamic nuclei while relative high values were measured in the medial geniculate body. Since a dramatic change in nucleoside concentrations occurs after death, the measured nucleoside concentrations are an interplay of original nucleotide and nucleoside concentrations and enzyme reactions following death. Thus our results suggest regional differences in nucleotide and nucleoside composition and nucleotide metabolising enzyme activities between brain areas.