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

Shared Gene Expression Alterations in Schizophrenia and Bipolar Disorder

“…Other studies (e.g., 15,[46][47][48] have found that subjects with BPD or SZ have decreased mitochondrial-associated transcripts. Many authors of microarray studies acknowledge that pH will influence mitochondrial gene expression, and when the effect is strongly controlled, such as in our microarray study and others (7,9,19), the magnitude of mitochondrial gene expression differences in SZ or BPD is markedly reduced. This same effect was seen in our study in which we found mitochondrial-related genes before ANCOVA, and after removing outlier chips and samples, there was a reduction in mitochondrial genes that were significant.…”

“…This ANCOVA was restricted to subjects above the median pH of 6.57 and with the covariates of pH and age. Although covariate analysis approach might be useful with the strong effect of pH, it may not be linear through the lower pH range, when subjects may show a ceiling or floor effect depending on the direction of association (7)(8)(9)(16)(17)(18)(19). Therefore, we attempted to use subjects with above-median pH as an indicator of fewer residual agonal effects.…”

Mitochondrial involvement in psychiatric disorders

“…In a third study, Mexal et al (2006) showed that hippocampal gene expression was highly dependent upon pH, especially for functional groups related to mitochondrial energy metabolism (68). Taken together, at least three independent microarray studies from different brain banks strongly support that pH differences in postmortem brain affects microarray gene expression for nuclear-encoded transcripts related to mitochondrial functions.…”

Selection of Reference Gene Expression in a Schizophrenia Brain Cohort

“…However, since RIN measures are only available after RNA isolation, we found that tissue pH can be used as a general guide to select potential controls to match to cases prior to RNA isolation [26,27]. Since cerebellar and cortical pH correlate, determining cerebellar pH may be a valuable first step in evaluating the suitability of cases for RNA analysis [26,28]; however, high tissue pH does not always indicate good RNA [26,27] and low pH does not necessarily yield low quality RNA. The current cut off for what is an acceptable RIN value varies considerably, with some studies suggesting that a moderate amount of degradation and a RIN as low as 3.8 to 4.0 may be usable [6,8,29].…”

“…Most brain banks attempt to collect cases with the shortest PMI possible, although researchers have challenged the importance of PMI in determining RNA quality [6,[30][31][32][33]. A number of studies suggest that PMI has no correlation or only a weak correlation with RNA quality [10,[26][27][28]. Studies which have examined human tissue collected during neurosurgery for epilepsy with minimal delay shows that the freshly acquired brain tissue pH and RIN are comparable or even lower to that collected postmortem [10,26].…”