Pre‐and Postmortem Influences on Brain RNA

Abstract

Many potentially valuable techniques for the understanding of human neurobiological and neuropathological processes require the use of RNA obtained from postmortem tissue. As with earlier neurochemical studies, there are two particular problems posed by such tissue in comparison with tissue from experimental animals. These are the postmortem interval and the condition of the patient prior to death, referred to as the agonal state. We review the nature and extent of the effects of postmortem interval and agonal state on RNA in brain tissue, with particular reference to the study of neuropsychiatric disorders. Perhaps surprisingly, postmortem interval has at most a modest effect on RNA. Abundant intact and biologically active RNA is present in tissue frozen 36 h or more after death. Postmortem interval does not account for the marked variability observed among human brains in all RNA parameters. Despite the overall stability of RNA after death, some evidence suggests that individual RNAs may undergo postmortem decay. Less attention has been paid to the effects of agonal state. The existing data indicate that events in the premortem period such as hypoxia and coma can affect the amount of some messenger RNAs. The nature of agonal state influences depends on the messenger RNA in question, though the basis for this selective vulnerability is unknown. No agonal state effect on overall RNA level or activity has been found. The data show that postmortem brain tissue can be used for RNA research. However, considerable attention must be paid to controlling for the influences of pre-and postmortem factors, especially when quantitative analyses are performed.

Post-mortem Interval Effects on the Phosphorylation of Signaling Proteins

“…Thus, it cannot be assumed that because one particular protein, mRNA, etc is stable, all are stable during a certain PMI. In addition to PMI and storage temperature, other factors such as agonal state at death (Bowen et al, 1976;Butterworth et al, 1983;Harrison et al, 1991;Lewis and Akil, 1997;Perry et al, 1977aPerry et al, , 1982Spokes, 1979;Yates et al, 1990), pH (generally related to agonal state) (Barton et al, 1993;Eastwood and Harrison, 2000;Harrison et al, 1995;Johnston et al, 1997;Kingsbury et al, 1995), freezing time (Roytta et al, 1980), and time or season of death (Bucht et al, 1981;Carlsson et al, 1980; Perry et al, 1977a-d), among many others, have been found to influence the degradationFor levelFof biological products in postmortem brain specimens. Thus, it remains critical to ascertain the post-mortem stability, and the stability under other conditions, of the biological product.…”

Increased mRNA Expression of α2A-Adrenoceptors, Serotonin Receptors and μ-Opioid Receptors in the Brains of Suicide Victims

“…However, when performing such analyses, several factors should be taken into account. Firstly, mRNA degradation after death can lead to the fragmentation of RNA species (Barton et al, 1993;Leonard et al, 1993). The longer the time spent by the corpses at high outdoor temperatures, the more severe mRNA degradation is.…”

Human postmortem tissue: What quality markers matter?

“…We have taken several of these newer measures of tissue quality and tested them in human postmortem tissue in a variety of situations to detect the relationship of the markers to the real quality of the postmortem tissue. Traditionally, a low postmortem interval (Barton et al, 1993;Ferrer-Alcon et al, 2003;Harrison et al, 1995;Lewis, 2002;Trotter et al, 2002) has been the hallmark of high tissue quality. More recently tissue pH (Hynd et al, 2003;Kingsbury et al, 1995;Li et al, 2004) has been used, and even more recently, specific markers of RNA quality have been introduced (Imbeaud et al, 2005;Johnston et al, 1997;Miller et al, 2004).…”