Pre- and postmortem influences on brain RNA.
Author(s): Barton AJ, Pearson RC, Najlerahim A, Harrison PJ
Publication: J Neurochem, 1993, Vol. 61, Page 1-11
PubMed ID: 7685811 PubMed Review Paper? Yes
Purpose of Paper
Conclusion of Paper
Studies
-
Study Purpose
The purpose of this study was to review the effects of PI (0-134 h) and patient condition on total RNA quantity and individual transcript abundance.
Summary of Findings:
Literature review shows that most studies have found no decline in total or Poly(A) mRNA in the first 36 h of postmortem interval. Beyond the first 36 h data is sparse and conflicting, with effects on poly(A) mRNA levels observed after a PMI of 36-48 h or no alterations observed after 134 h PMI. The detection of full length RNA by northern blots and in vitro translation indicate that at least in most cases intact mRNA is present until PMI of 36 h. Many studies have also investigated the effects of PMI on individual transcripts by northern blot, ISH, RT-PCR and RNAse protection assays. Most individual transcripts were not affected by PMI; however northern blots revealed changes in NF-L, alpha-tubulin and GFAP between specimens with PMIs of 0.7 h and 13.5 h in one report. These changes were not repeatable in other studies examining the same transcripts over a much longer PMI. PNMT, APP were also reduced in RT-PCR assays between 2.9 h and 22.7 h PMI, although the APP finding has not been replicated using other methods. The authors conclude that a PMI of up to 36 h does not impact total RNA levels, but further studies are needed to understand the effects on individual transcripts in specimens after longer PMI.
Biospecimens
Preservative Types
- Frozen
Diagnoses:
- Not specified
- Alzheimer's Disease
Platform:
Analyte Technology Platform RNA In situ hybridization RNA Northern blot RNA RT-PCR RNA In vitro translation RNA Spectrophotometry Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Preaquisition Postmortem interval 0-134 h
RT-PCR Specific Targeted nucleic acid PNMT
APP
beta-Actin
Northern blot Specific Targeted nucleic acid NF-L
GFAP
alpha-tubulin
beta-Actin
-
Study Purpose
The purpose of this study was to review the effects of coma, hypoxia, fever, infection, and seizures on RNA transcript levels.
Summary of Findings:
The effects of patient condition are difficult to extrapolate as often conditions represent a complex combination of events and diagnoses, but studies have shown that factors such as coma, hypoxia, and seizures can impact transcript amount. Terminal coma has been shown to cause a reduction in the m1 muscarinic receptor in the temporal cortex. The activity of glutamate decarboxylase was also correlated to coma duration (1-336 h). In a study that categorized patient condition post-mortem, poor patient condition reduced glutamate receptors, although details pertaining to the classification were not included in the present review. Hypoxia and seizures, but not coma, fever, or infection, impact specific transcript levels in brainstem, although these transcripts were not identified in the present review. The authors conclude that patient condition does impact individual mRNA abundance and that further studies are necessary to elucidate these changes.
Biospecimens
Preservative Types
- Frozen
Diagnoses:
- Not specified
- Alzheimer's Disease
Platform:
Analyte Technology Platform RNA In situ hybridization RNA Northern blot RNA RT-PCR Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Preaquisition Rapidity of death 1-336 h
Preaquisition Prior patient medical condition Coma
Seizure
Fever
Infection
Hypoxia