THE RELATIVE IMPORTANCE OF PREMORTEM ACIDOSIS AND POSTMORTEM INTERVALFOR HUMAN BRAIN GENE-EXPRESSION STUDIES - SELECTIVE MESSENGER-RNA VULNERABILITY AND COMPARISON WITH THEIR ENCODED PROTEINS

To help account for the variable quality and quantity of RNA in human brain, we have studied the effect of premortem (agonal state) and post mortem factors on the detection of poly(A)(+)mRNA and eight mRNAs, For comparison, the influence of the same factors upon gene products enco ded by the mRNAs was studied immunocytochemically or by receptor autor adiography. Brain pH declined with increasing age at death and was rel ated to agonal state severity, but was independent of postmortem inter val and the histological presence of hypoxic changes. By linear regres sion, 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 mR NAs; however, RNA content was reduced by 40% at 96 h after death. pH i s superior to clinical assessments of agonal state or mode of death in predicting mRNA preservation. It provides a simple means to improve h uman brain gene expression studies. pH is stable after death and durin g freezer storage and can be measured either in cerebrospinal fluid or in homogenised tissue.