Concentration of nucleosides and related compounds in cerebral and cerebellar cortical areas and white matter of the human brain

Abstract

1. Nucleosides potentially participate in the neuronal functions of the brain. However, their distribution and changes in their concentrations in the human brain is not known. For better understanding of nucleoside functions, changes of nucleoside concentrations by age and a complete map of nucleoside levels in the human brain are actual requirements. 2. We used post mortem human brain samples in the experiments and applied a recently modified HPLC method for the measurement of nucleosides. To estimate concentrations and patterns of nucleosides in alive human brain we used a recently developed reverse extrapolation method and multivariate statistical analyses. 3. We analyzed four nucleosides and three nucleobases in human cerebellar, cerebral cortices and in white matter in young and old adults. Average concentrations of the 308 samples investigated (mean+/-SEM) were the following (pmol/mg wet tissue weight): adenosine 10.3+/-0.6, inosine 69.5+/-1.7, guanosine 13.5+/-0.4, uridine 52.4+/-1.2, uracil 8.4+/-0.3, hypoxanthine 108.6+/-2.0 and xanthine 54.8+/-1.3. We also demonstrated that concentrations of inosine and adenosine in the cerebral cortex and guanosine in the cerebral white matter are age-dependent. 4. Using multivariate statistical analyses and degradation coefficients, we present an uneven regional distribution of nucleosides in the human brain. The methods presented here allow to creation of a nucleoside map of the human brain by measuring the concentration of nucleosides in microdissected tissue samples. Our data support a functional role for nucleosides in the brain.

Fig. 1.

Chromatograms of representative samples from the cerebellar cortex (CEREBELLAR CTX.), cerebral white matter and occipital cortical areas (CEREBRAL WHITE MATTER, OCCIPITAL CTX) are shown. The UV absorbance values are normalised to 1 mg w.w. sample. Concentrations of several other nucleosides, like deoxyuridine, deoxyadenosine etc. were detectable in some but not all samples, therefore they were excluded from further statistical analysis. CTX: cortex.

Fig. 2.

(A) The hierarchical cluster structure. Clusters: I: cerebellum, II: white matter, III: cerebral cortex; c: cortex, flocc.-nod l.: flocculo-nodular lobe, w: white matter, somatom. c.: somatomotor cortex, somatos. c.: somatosensory cortex. (B) The scatterplot of the brain samples in the three-dimensional discriminant function space. The clusters are the same as in (A). CTX: cortex.