Postmortem delay has minimal effect on brain RNA integrity

Postmortem delay has minimal effect on brain RNA integrity
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DOI:
10.1097/nen.0b013e31815c196a
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发表时间:
2007-12-01
影响因子:
3.2
通讯作者:
Hulette, Christine M.
Hulette, Christine M.
中科院分区:
医学4区
文献类型:
--
作者:
Ervin, John F.;Heinzen, Erin L.;Hulette, Christine M.

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布莱恩阿尔茨海默病研究中心从阿尔茨海默病 (AD) 患者和认知正常对照受试者身上获取死后人类脑组织,用于分子和遗传研究项目。越来越多的研究表明,基因转录水平的变化可能导致疾病的发生和进展。确定基因表达调控如何影响 AD 需要使用来自人类大脑库的高质量 mRNA。本研究的目的是确定现有脑组织库的质量和适用性,以用于未来的基因表达研究。我们选择了 32 例 Braak IV、V 或 VI 期 AD 病例。在可能的情况下,将这些 AD 病例与 36 名正常对照病例按年龄和性别进行匹配。对每个大脑的多个区域进行了采样,包括额叶皮层、颞叶皮层、枕叶皮层和小脑。 14 个对照病例的海马体也可用于研究。分析了几个死前和死后变量的比较,例如死后间隔、临终状态、脑室脑脊液 pH 值和死亡原因。从每个大脑的至少 I 个区域中分离出 RNA,并且大多数大脑从所有测试区域中产生了完整的 RNA。对临床变量的分析没有揭示任何与恢复完整 mRNA 的能力相关的特征。我们得出的结论是,在死后数小时内,未降解的 mRNA 可能从大多数大脑区域中分离出来,并且脑室液的 pH 值和死后间隔都不能预测 mRNA 的完整性。
The Bryan Alzheimer Disease Research Center obtains postmortem human brain tissue from patients with Alzheimer disease (AD) and cognitively normal control subjects for molecular and genetic research programs. A growing body of research suggests that variations in gene transcript levels may contribute to the onset and progression of disease. Identifying how the regulation of gene expression may affect AD requires the use of high-quality mRNA from banked human brains. The present study was conducted to establish the quality and suitability of available banked brain tissue for future gene expression studies. We chose 32 AD cases with Braak stage IV, V, or VI. These AD cases were matched to 36 normal control cases by age and sex when possible. Multiple regions from each brain were sampled, including frontal cortex, temporal cortex, occipital cortex, and cerebellum. Hippocampus was also available for study from 14 control cases. A comparison of several antemortem and postmortem variables, such as postmortem interval, agonal state, ventricular cerebrospinal fluid pH, and cause of death were analyzed. RNA was isolated from at least I area from every brain and most brains yielded intact RNA from all regions tested. Analysis of the clinical variables did not reveal any features that correlated with the ability to recover intact mRNA. We conclude that undegraded mRNA may be isolated from most brain regions many hours postmortem and that neither the pH of ventricular fluid nor postmortem interval is predictive of mRNA integrity.