Brain pH has a significant impact on human postmortem hippocampal gene expression profiles.

Author(s): Mexal S, Berger R, Adams C E, Ross R G, Freedman R, Leonard S

Publication: Brain Res, 2006, Vol. 1106, Page 1

PubMed ID: 16843448 PubMed Review Paper? No

Purpose of Paper

Conclusion of Paper

Studies

1. Study Purpose

   The purpose of this study was to assess whether pH is consistent across brain regions in human postmortem tissue and to assess whether pre- and postmortem factors correlate with brain pH or RNA quality (as measured by the 3'/5' ratios of beta-actin and GAPDH).

   Summary of Findings:

   The authors reported that pH was comparable across the seven brain regions evaluated; cortical pH correlated most closely with hippocampal pH. Brain pH did not correlate with smoking status, patient diagnosis of schizophrenia, patient age, or postmortem interval. Brain pH was significantly higher in patients who had suffered a rapid death than in patients who had experienced a prolonged agonal state. RNA quality correlated with brain pH but not other evaluated factors, including patient age, patient agonal state, patient diagnosis of schizophrenia, patient smoking status, postmortem interval, or biospecimen storage duration.

   Biospecimens

   • Tissue - Brain

   Preservative Types

   • Frozen

   Diagnoses:

   • Schizophrenia
   • Autopsy
   • Not specified

   Platform:

   Analyte	Technology Platform
   RNA	DNA microarray
   RNA	Electrophoresis
   RNA	Real-time qRT-PCR

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Preaquisition	Patient gender	Female Male
   Biospecimen Acquisition	Biospecimen location	Brain stem Caudate Temporal Cortex Hippocampus Cerebellum Cingulate Thalamus
   Preaquisition	Diagnosis/ patient condition	Schizophrenia No history of mental illness
   Storage	Storage duration	25.5 +/- 16.6 months 6.2 +/- 7.5 months 10.31 +/- 5.2 months 25.1 +/- 27.6 months
   Preaquisition	Patient age	23 - 88 years
   Preaquisition	Postmortem interval	12.6 - 15.9 h
   Preaquisition	Rapidity of death	Agonal score of 1 or 2 (rapid death) Agonal score of 3 or 4 (prolonged death)
   Preaquisition	Diagnosis/ patient condition	Smoker Non-smoker

   View more

2. Study Purpose

   The purpose of this study was to determine if expression analysis of identified pH-influenced genes can discriminate among low and high pH brain tissues using an independent sample set.

   Summary of Findings:

   The authors report successfully employing a training set of high-pH (>6.54), high-quality-RNA tissues and low-pH (<6.54), low-quality-RNA tissues to identify 94 transcripts that were differentially expressed between groups; 73% were significantly down-regulated in specimens in the low pH group. These transcripts appeared to be related to mitochondrial energy metabolism. In a test set of ten specimens, this set of transcripts successfully identified high and low pH tissues.

   Biospecimens

   • Tissue - Brain

   Preservative Types

   • Frozen

   Diagnoses:

   • Schizophrenia
   • Autopsy
   • Not specified

   Platform:

   Analyte	Technology Platform
   RNA	DNA microarray

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Preaquisition	Diagnosis/ patient condition	Schizophrenia No history of mental illness
   Biospecimen Aliquots and Components	pH	Brain pH >6.54 Brain pH <6.54
   DNA microarray Specific	Quality metrics	GAPDH 3'/5' ratio Beta-actin 3'/5' ratio

   View more