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

1. 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

   • Tissue - Brain

   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

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2. 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

   • Tissue - Brain

   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

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