NIH, National Cancer Institute, Division of Cancer Treatment and Diagnosis (DCTD) NIH - National Institutes of Health National Cancer Institute DCTD - Division of Cancer Treatment and Diagnosis

Effect of pre- and postmortem variables on specific mRNA levels in human brain.

Author(s): Burke W J, O'Malley K L, Chung H D, Harmon S K, Miller J P, Berg L

Publication: Brain Res Mol Brain Res, 1991, Vol. 11, Page 37

PubMed ID: 1662743 PubMed Review Paper? No

Purpose of Paper

The purpose of this paper was to determine the influence of premortem variables (age at death, coma, fever, systemic infection, low blood pressure, hypoxia, seizure, or use of a respirator) and postmortem variables (postmortem interval, storage duration) on mRNA species stability in brain as determined by reverse transcription polymerase chain reaction (RT-PCR) and Southern blot analyses.

Conclusion of Paper

The authors report gene-dependent effects in expression as a result of antemortem (hypoxia, seizure activity) and postmortem (postmortem interval, storage duration, and the interval between death and body refrigeration) variables. They therefore recommend that attention be paid to pre- and postmortem variables, and the influence of specific factors on RNAs of interest be established prior to comparison of mRNA levels among different disease states.

Studies

  1. Study Purpose

    Polymerase chain reaction (PCR) was used to investigate which of eight pre- and four postmortem factors affect the stability of PNMT, three splice forms of APP (APP695, APP751, and APP770) and beta-actin mRNAs in the C1 region in the rostral ventral lateral medulla of human autopsy brain.

    Summary of Findings:

    The authors report that of the eight premortem variables examined, hypoxia was associated with decreased levels of PNMT and seizure activity was associated with increased levels of APP751. Of the four postmortem variables examined, postmortem interval and storage interval correlated with depressed levels of APP751 and beta-actin. The death refrigeration interval correlated with increased levels of total APP and APP695.

    Biospecimens
    Preservative Types
    • Frozen
    Diagnoses:
    • Autopsy
    • Not specified
    Platform:
    AnalyteTechnology Platform
    DNA Southern blot
    RNA RT-PCR
    Pre-analytical Factors:
    ClassificationPre-analytical FactorValue(s)
    Preaquisition Patient age 32 y
    34 y
    37 y
    43 y
    57 y
    61 y
    63 y
    64 y
    71 y
    72 y
    Preaquisition Diagnosis/ patient condition Fever
    No fever
    Systemic infection
    No systemic infection
    Seizure activity
    No seizure activity
    Hypoxia
    No hypoxia
    0 hours in coma
    0.1 hours in coma
    0.2 hours in coma
    0.3 hours in coma
    0.5 hours in coma
    0.8 hours in coma
    2.0 hours in coma
    2.3 hours in coma
    6.8 hours in coma
    30.6 hours in coma
    On a respirator
    Not on a respirator
    Preaquisition Diagnosis/ patient condition Systemic infection
    No systemic infection
    Preaquisition Blood pressure Hypotension
    No hypotension
    Preaquisition Diagnosis/ patient condition On a respirator
    Not on a respirator
    Preaquisition Diagnosis/ patient condition Seizure activity
    No seizure activity
    Preaquisition Diagnosis/ patient condition Hypoxia
    No hypoxia
    0 hours in coma
    0.1 hours in coma
    0.2 hours in coma
    0.3 hours in coma
    0.5 hours in coma
    0.8 hours in coma
    2.0 hours in coma
    2.3 hours in coma
    6.8 hours in coma
    30.6 hours in coma
    Preaquisition Postmortem interval 2.9 h
    4.2 h
    4.3 h
    7.0 h
    8.4 h
    14.3 h
    17.3 h
    17.6 h
    20 h
    24.7 h
    3.1 h PMI + coma
    7.0 h PMI + coma
    8.7 h PMI + coma
    11.0 h PMI + coma
    14.8 h PMI + coma
    18.4 h PMI + coma
    19.6 h PMI + coma
    20.1 h PMI + coma
    24.7 h PMI + coma
    34.9 h PMI + coma
    Storage Storage duration 8 days
    23 days
    24 days
    32 days
    221 days
    235 days
    396 days
    500 days
    1221 days
    1229 days
    Preaquisition Postmortem interval 3.1 h PMI + coma
    7.0 h PMI + coma
    8.7 h PMI + coma
    11.0 h PMI + coma
    14.8 h PMI + coma
    18.4 h PMI + coma
    19.6 h PMI + coma
    20.1 h PMI + coma
    24.7 h PMI + coma
    34.9 h PMI + coma
    Preaquisition Postmortem condition(s) 0-4 h before refrigeration
    1-22 h refrigerated

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