Effect of agonal and postmortem factors on gene expression profile: quality control in microarray analyses of postmortem human brain

There are major concerns that specific agonal conditions, including coma and hypoxia, might affect ribonucleic acid (RNA) integrity in postmortem brain studies. We report that agonal factors significantly affect RNA integrity and have a major impact on gene expression profiles in microarrays. In contrast to agonal factors, gender, age, and postmortem factors have less effect on gene expression profiles. The Average Correlation Index is proposed as a method for evaluating RNA integrity on the basis of similarity of microarray profiles. Reducing the variance due to agonal factors is critical in investigating small but validated gene expression differences in messenger RNA levels between psychiatric patients and control subjects.

[1]  Paul J. Harrison,et al.  Regional and neuronal reductions of polyadenylated messenger RNA in Alzheimer's disease , 1991, Psychological Medicine.

[2]  M. Casanova,et al.  Biological stability of mRNA isolated from human postmortem brain collections , 1993, Biological Psychiatry.

[3]  S. Whatley,et al.  Characterisation of messenger RNA extracted post-mortem from the brains of schizophrenic, depressed and control subjects. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[4]  C D Marsden,et al.  Tissue pH as an indicator of mRNA preservation in human post-mortem brain. , 1995, Brain research. Molecular brain research.

[5]  C. Finch,et al.  Extensive postmortem stability of RNA from rat and human brain , 1986, Journal of neuroscience research.

[6]  R. Myers,et al.  Gender-Specific Gene Expression in Post-Mortem Human Brain: Localization to Sex Chromosomes , 2004, Neuropsychopharmacology.

[7]  Huda Akil,et al.  Microarray technology: a review of new strategies to discover candidate vulnerability genes in psychiatric disorders. , 2003, The American journal of psychiatry.

[8]  J. Sleigh,et al.  Amoxapine Overdose: Recovery after Severe Metabolic Acidosis (pH 6.69) and Status Epilepticus , 1990, Anaesthesia and intensive care.

[9]  J. Hardy,et al.  Agonal status affects the metabolic activity of nerve endings isolated from postmortem human brain. , 1985, Neurochemical pathology.

[10]  Paul J. Harrison,et al.  Terminal coma affects messenger RNA detection in post mortem human temporal cortex. , 1991, Brain research. Molecular brain research.

[11]  R. Mailman,et al.  Postmortem stability of dopamine D1 receptor mRNA and D1 receptors. , 1993, Brain research. Molecular brain research.

[12]  Paul J. Harrison,et al.  The Effects of Alzheimer's Disease, Other Dementias, and Premortem Course on β‐Amyloid Precursor Protein Messenger RNA in Frontal Cortex , 1994, Journal of neurochemistry.

[13]  Paul J. Harrison,et al.  The relative importance of premortem acidosis and postmortem interval for human brain gene expression studies: selective mRNA vulnerability and comparison with their encoded proteins , 1995, Neuroscience Letters.

[14]  Dorothea K. Thompson,et al.  DNA Microarray Technology , 2005 .

[15]  R. Yolken,et al.  Multivariate analysis of RNA levels from postmortem human brains as measured by three different methods of RT-PCR , 1997, Journal of Neuroscience Methods.

[16]  B. Winblad,et al.  The patients dying after long terminal phase have acidotic brains; implications for biochemical measurements on autopsy tissue , 2005, Journal of Neural Transmission.

[17]  W. Griffin,et al.  The isolation and in vitro translation of undegraded messenger RNAs from human postmortem brain. , 1981, Analytical biochemistry.

[18]  S. Pardue,et al.  Heat‐Shock 70 Messenger RNA Levels in Human Brain: Correlation with Agonal Fever , 1995, Journal of neurochemistry.

[19]  R. Ravid,et al.  Brain banking and the human hypothalamus--factors to match for, pitfalls and potentials. , 1992, Progress in brain research.

[20]  J. Miller,et al.  Effect of pre- and postmortem variables on specific mRNA levels in human brain. , 1991, Brain research. Molecular brain research.

[21]  D. G. Standaert,et al.  Gene expression profiling in the post-mortem human brain — no cause for dismay , 2001, Journal of Chemical Neuroanatomy.

[22]  Paul J. Harrison,et al.  Pre‐and Postmortem Influences on Brain RNA , 1993, Journal of neurochemistry.

[23]  S. Pardue,et al.  Selective postmortem degradation of inducible heat shock protein 70 (hsp70) mRNAs in rat Brain , 1994, Cellular and Molecular Neurobiology.

[24]  A. Thomson,et al.  mRNA Stability and the Control of Gene Expression: Implications for Human Disease , 2002, Neurochemical Research.

[25]  Yasuhiro Yamamoto,et al.  Measurements of cortical cellular pH by intracranial tonometer in severe head injury , 2000, Critical care medicine.

[26]  Richard Weindruch,et al.  Gene-expression profile of the ageing brain in mice , 2000, Nature Genetics.

[27]  J. Albrecht,et al.  Effect of anoxia and ischemia on ribonuclease activity in brain , 1979, Journal of Neurochemistry.

[28]  S. Liebhaber.  mRNA stability and the control of gene expression. , 2007, Nucleic acids symposium series.

[29]  James P. Bennett,et al.  Stability of gene expression in postmortem brain revealed by cDNA gene array analysis , 2002, Brain Research.

[30]  F. H. Schmidt,et al.  The role of mRNA and protein stability in gene expression , 1989, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[31]  T. Speed,et al.  Summaries of Affymetrix GeneChip probe level data. , 2003, Nucleic acids research.

[32]  Pat Levitt,et al.  Analysis of complex brain disorders with gene expression microarrays: schizophrenia as a disease of the synapse , 2001, Trends in Neurosciences.

[33]  P. Dodd,et al.  Biochemical and molecular studies using human autopsy brain tissue , 2003, Journal of neurochemistry.

[34]  K. Boer,et al.  THE PRESENCE OF BIOLOGICALLY LABILE COMPOUNDS DURING ISCHEMIA AND THEIR RELATIONSHIP TO THE EEG IN RAT CEREBRAL CORTEX AND HYPOTHALAMUS , 1972, Journal of neurochemistry.

[35]  W H Wong,et al.  Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia , 2001, Proceedings of the National Academy of Sciences of the United States of America.