Quantifying mRNA in postmortem human brain: influence of gender, age at death, postmortem interval, brain pH, agonal state and inter-lobe mRNA variance

Preece, Paul; Cairns, Nigel J.

doi:10.1016/s0169-328x(03)00337-1

Cited by 191 publications

(154 citation statements)

References 21 publications

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“…Several laboratories have approached the evaluation of human postmortem brain cases with suggestions for markers of tissue quality (Lee et al, 2005;Preece and Cairns, 2003;Tomita et al, 2004). 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.…”

Section: Introductionmentioning

confidence: 99%

Human postmortem tissue: What quality markers matter?

Ghose²,

et al. 2006

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Post mortem human brain tissue is used for the study of many different brain diseases. A key factor in conducting postmortem research is the quality of the tissue. Unlike animal tissue, whose condition at death can be controlled and influenced, human tissue can only be collected naturalistically. This introduces potential confounds, based both on pre-and postmortem conditions, that may influence the quality of tissue and its ability to yield accurate results. The traditionally recognized confounds that reduce tissue quality are agonal factors (e.g., coma, hypoxia, hyperpyrexia at the time of death), and long postmortem interval (PMI). We measured tissue quality parameters in over 100 postmortem cases collected from different sources and correlated them with RNA quality (as indicated by the RNA Integrity Number (RIN)) and with protein quality (as measured by the level of representative proteins). Our results show that the most sensible indicator of tissue quality is RIN and that there is a good correlation between RIN and the pH. No correlation developed between protein levels and the aforementioned factors. Moreover, even when RNA was degraded, the protein levels remained stable. However, these correlations did not prove true under all circumstances (e.g. thawed tissue, surgical tissue), that yielded unexpected quality indicators. These data also suggest that cases whose source was a Medical Examiner's office represent high tissue quality.

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Section: Introductionmentioning

confidence: 99%

Human postmortem tissue: What quality markers matter?

Ghose²,

et al. 2006

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“…Many parameters of brain function and structure vary between men and women (eg Gur et al, 1995;Murphy et al, 1996;De Courten-Myers, 1999;De Bellis et al, 2001;Goldstein et al, 2001;Preece and Cairns, 2003;De Vries, 2004), and most psychiatric disorders show sex differences in one or more variables including incidence, age at onset, clinical features, and outcome (eg Lensi et al, 1996;Tamminga, 1997;Piccinelli and Wilkinson, 2000;Aleman et al, 2003;Baron-Cohen et al, 2005). These dimorphisms are usually ascribed primarily to the influence of sex hormones (Collaer and Hines, 1995;Rubinow and Schmidt, 1996;Seeman, 1997;Kelly et al, 1999), as well as to the actions of sex chromosome genes (Vawter et al, 2004;Cutter et al, 2006;Davies and Wilkinson, 2006).…”

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confidence: 99%

Catechol-O-Methyltransferase (COMT): A Gene Contributing to Sex Differences in Brain Function, and to Sexual Dimorphism in the Predisposition to Psychiatric Disorders

Harrison

Tunbridge

2007

Neuropsychopharmacol

273

217

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Sex differences in the genetic epidemiology and clinical features of psychiatric disorders are well recognized, but the individual genes contributing to these effects have rarely been identified. Catechol-O-methyltransferase (COMT), which metabolizes catechol compounds, notably dopamine, is a leading candidate. COMT enzyme activity, and the neurochemistry and behavior of COMT null mice, are both markedly sexually dimorphic. Genetic associations between COMT and various psychiatric phenotypes frequently show differences between men and women. Many of these differences are unconfirmed or minor, but some appear to be of reasonable robustness and magnitude; eg the functional Val 158 Met polymorphism in COMT is associated with obsessive-compulsive disorder in men, with anxiety phenotypes in women, and has a greater impact on cognitive function in boys than girls. Sex-specific effects of COMT are usually attributed to transcriptional regulation by estrogens; however, additional mechanisms are likely to be at least as important. Here we review the evidence for a sexually dimorphic influence of COMT upon psychiatric phenotypes, and discuss its potential basis. We conclude that despite the evidence being incomplete, and lacking a unifying explanation, there are accumulating and in places compelling data showing that COMT differentially impacts on brain function and dysfunction in men and women. Since sex differences in the genetic architecture of quantitative traits are the rule not the exception, we anticipate that additional evidence will emerge for sexual dimorphisms, not only in COMT but also in many other autosomal genes.

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“…This is primarily due to the fact that postmortem human tissues are heterogeneous. Postmortem intervals and conditions as well as antemortem factors such as age, gender, body mass, and the physiological/pathological conditions of the agonal phase can profoundly affect expression profiles and half-lives of certain gene transcripts in postmortem tissues, obscuring the employment of molecular biomarkers to investigate the cause and process of death (Durrenberger et al, 2010;Preece and Cairns, 2003;Tomita et al, 2004). Therefore, data normalization and RNA integrity have been essential issues in the field of forensic molecular pathology (Vennemann and Koppelkamm, 2010b).…”

Section: Discussionmentioning

confidence: 99%

Quantitative Analyses of Postmortem Heat Shock Protein mRNA Profiles in the Occipital Lobes of Human Cerebral Cortices: Implications in Cause of Death

Chung

Seo

Kim

et al. 2012

Molecules and Cells

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Quantitative RNA analyses of autopsy materials to diagnose the cause and mechanism of death are challenging tasks in the field of forensic molecular pathology. Alterations in mRNA profiles can be induced by cellular stress responses during supravital reactions as well as by lethal insults at the time of death. Here, we demonstrate that several gene transcripts encoding heat shock proteins (HSPs), a gene family primarily responsible for cellular stress responses, can be differentially expressed in the occipital region of postmortem human cerebral cortices with regard to the cause of death. HSPA2 mRNA levels were higher in subjects who died due to mechanical asphyxiation (ASP), compared with those who died by traumatic injury (TI). By contrast, HSPA7 and A13 gene transcripts were much higher in the TI group than in the ASP and sudden cardiac death (SCD) groups. More importantly, relative abundances between such HSP mRNA species exhibit a stronger correlation to, and thus provide more discriminative information on, the death process than does routine normalization to a housekeeping gene. Therefore, the present study proposes alterations in HSP mRNA composition in the occipital lobe as potential forensic biological markers, which may implicate the cause and process of death.

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Quantifying mRNA in postmortem human brain: influence of gender, age at death, postmortem interval, brain pH, agonal state and inter-lobe mRNA variance

Cited by 191 publications

References 21 publications

Human postmortem tissue: What quality markers matter?

Human postmortem tissue: What quality markers matter?

Catechol-O-Methyltransferase (COMT): A Gene Contributing to Sex Differences in Brain Function, and to Sexual Dimorphism in the Predisposition to Psychiatric Disorders

Quantitative Analyses of Postmortem Heat Shock Protein mRNA Profiles in the Occipital Lobes of Human Cerebral Cortices: Implications in Cause of Death

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