Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
Neuropathol Appl Neurobiol. 2010 Oct;36(6):498-504. doi: 10.1111/j.1365-2990.2010.01098.x.
Many variables affect mRNA measurements in post mortem human brain tissue. Brain weight has not hitherto been considered to be such a factor. This study examined whether there is any relationship between brain weight and mRNA abundance.
We investigated quantitative real-time RT-PCR data for five 'housekeeping genes' using the 104 adult brains of the Stanley Microarray Consortium series. Eleven data sets were analysed, from cerebellum, hippocampus, and anterior cingulate cortex. We used a specified sequence of correlations, partial correlations and multiple regression analyses.
Brain weight correlated with the 'raw' (i.e. non-normalized) data for two mRNAs, β2-microglobulin and TATA-binding protein, measured in cerebellum and hippocampus, respectively. In hippocampus, the geometric mean of three housekeeping gene transcripts also correlated with brain weight. The correlations were significant after adjusting for age, sex and other confounders, and the effect of brain weight was confirmed using multiple regression. No correlations with brain weight were seen in the anterior cingulate cortex, nor for the other mRNAs examined.
The findings were not anticipated; they need replication in another brain series, and a more systematic survey is indicated. In the interim, we suggest that quantitative gene expression studies in human brain should inspect for a potential influence of brain weight, especially as the affected transcripts are commonly used as reference genes for normalization purposes in studies of neurological and psychiatric disorders. The relationship of brain weight with β2-microglobulin mRNA may reflect the roles of major histocompatibility complex class I genes in synapse formation and plasticity.
许多变量会影响人死后脑组织中的 mRNA 测量。到目前为止，脑重量尚未被认为是一个这样的因素。本研究检查了脑重量与 mRNA 丰度之间是否存在任何关系。
我们使用斯坦利微阵列联盟系列的 104 个成人脑研究了五个“管家基因”的定量实时 RT-PCR 数据。分析了来自小脑、海马体和前扣带回皮层的 11 个数据集。我们使用了特定的相关性、偏相关性和多元回归分析序列。
脑重量与小脑和海马体中分别测量的两个 mRNA（β2-微球蛋白和 TATA 结合蛋白）的“原始”（即未标准化）数据相关。在海马体中，三种管家基因转录本的几何平均值也与脑重量相关。在调整年龄、性别和其他混杂因素后，相关性仍然显著，并且使用多元回归确认了脑重量的影响。在前扣带回皮层中没有发现与脑重量相关的相关性，也没有发现与其他检查的 mRNA 相关的相关性。
这些发现出人意料；它们需要在另一个脑系列中进行复制，并且需要进行更系统的调查。在此期间，我们建议在人类大脑的定量基因表达研究中应检查脑重量的潜在影响，特别是因为受影响的转录本通常被用作神经和精神疾病研究中标准化目的的参考基因。脑重量与β2-微球蛋白 mRNA 的关系可能反映了主要组织相容性复合物 I 基因在突触形成和可塑性中的作用。
