The relative importance of premortem acidosis and postmortem interval for human brain gene expression studies: selective mRNA vulnerability and comparison with their encoded proteins
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Abstract
To help account for the variable quality and quantity of RNA in human brain, we have
studied the effect of premortem (agonal state) and postmortem factors on the detection
of poly(A)+mRNA and eight mRNAs. For comparison, the influence of the same factors
upon gene products encoded by the mRNAs was studied immunocytochemically or by receptor
autoradiography. Brain pH declined with increasing age at death and was related to
agonal state severity, but was independent of postmortem interval and the histological
presence of hypoxic changes. By linear regression, pH was significantly associated
with the abundance of several of the RNAs, but not with poly(A)+mRNA, immunoreactivities,
or binding site densities. Postmortem interval had a limited influence upon mRNA and
protein products. Freezer storage time showed no effect. Parallel rat brain studies
showed no relationship between postmortem interval (0-48 h) and amounts of total RNA,
poly(A)+RNA, or two individual mRNAs; however, RNA content was reduced by 40% at 96
h after death. pH is superior to clinical assessments of agonal state or mode of death
in predicting mRNA preservation. It provides a simple means to improve human brain
gene expression studies. pH is stable after death and during freezer storage and can
be measured either in cerebrospinal fluid or in homogenised tissue.