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

Concentration of nucleosides and related compounds in cerebral and cerebellar cortical areas and white matter of the human brain
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DOI:
10.1007/s10571-006-9103-3
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发表时间:
2006-07-01
影响因子:
4
通讯作者:
Palkovits, Miklos
Palkovits, Miklos
中科院分区:
医学3区
文献类型:
--
作者:
Kekesi, Katalin A.;Kovacs, Zsolt;Palkovits, Miklos

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1.核苷潜在地参与大脑的神经元功能。然而,它们在人脑中的分布和浓度变化尚不清楚。为了更好地了解核苷的功能,核苷浓度随年龄的变化和人脑中核苷水平的完整图谱是实际需要。我们在实验中使用死后人脑样品,并应用最近修改的HPLC方法测量核苷。为了估计活体人脑中核苷的浓度和模式,我们使用了最近发展的反向外推法和多元统计分析.我们分析了四个核苷和三个核碱基在人类小脑,大脑皮质和白色物质在年轻人和老年人。调查的308份样品的平均浓度(平均值+/- SEM)如下(pmol/mg湿组织重量):腺苷10.3 +/- 0.6,肌苷69.5 +/- 1.7,鸟苷13.5 +/- 0.4,尿苷52.4 +/- 1.2,尿嘧啶8.4 +/- 10.3,次黄嘌呤108.6 ± 2.0和黄嘌呤54.8 ± 1.3。我们还证明了大脑皮层中肌苷和腺苷以及大脑白色物质中鸟苷的浓度具有年龄依赖性。使用多元统计分析和降解系数,我们提出了一个不均匀的区域分布的核苷在人脑中。本文提出的方法允许通过测量显微组织样本中核苷的浓度来创建人脑的核苷图谱。我们的数据支持核苷在大脑中的功能作用。
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 +/- 10.3, 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.