Brain pH has a significant impact on human postmortem hippocampal gene expression profiles.
Studies of neurobiological disorders in the brain, including schizophrenia, rely on the use of postmortem brain tissues, in which an understanding of the effects of various pre- and postmortem variables on gene expression is critical. In several different brain regions, pH has been shown to have a large effect on postmortem brain gene expression patterns. One region that has not yet been evaluated in such studies is the hippocampus, a region often implicated in schizophrenia research. In the present study, we show that postmortem brain pH is similar across different brain regions. Brain pH accounted for greater variation in hippocampal gene expression profiles than any other parameter evaluated, including gender and schizophrenia. The predictive value of brain pH in an independent sample set was also greater than the disease, demonstrating that pH represents one of the most important control parameters in human postmortem gene expression studies in schizophrenia.
Mexal
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S
Department of Psychiatry, University of Colorado at Denver and Health Sciences Center, Mail Stop 8344, PO Box 6511, Aurora, CO 80045, USA.
Berger
R
R
Department of Psychiatry, University of Colorado at Denver and Health Sciences Center, Mail Stop 8344, PO Box 6511, Aurora, CO 80045, USA.
Adams
C E
CE
Department of Psychiatry, University of Colorado at Denver and Health Sciences Center, Mail Stop 8344, PO Box 6511, Aurora, CO 80045, USA.
Ross
R G
RG
Department of Psychiatry, University of Colorado at Denver and Health Sciences Center, Mail Stop 8344, PO Box 6511, Aurora, CO 80045, USA.
Freedman
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R
Veterans Affairs Medical Research Center, Denver, CO 80220, USA; Department of Psychiatry, University of Colorado at Denver and Health Sciences Center, Mail Stop 8344, PO Box 6511, Aurora, CO 80045, USA.
Leonard
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S
Veterans Affairs Medical Research Center, Denver, CO 80220, USA; Department of Psychiatry, University of Colorado at Denver and Health Sciences Center, Mail Stop 8344, PO Box 6511, Aurora, CO 80045, USA. Electronic address: Sherry.Leonard@UCHSC.edu.
D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods; D006624:Hippocampus / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011180:Postmortem Changes; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger