Analysis of gene expression in the rat hippocampus using real time PCR reveals high inter‐individual variation in mRNA expression levels

Abstract

In mammals, gene transcription is a step subjected to tight regulation mechanisms. In fact, changes in mRNA levels in the central nervous system (CNS) can account for numerous phenotypic differences in brain function. We performed a high-resolution analysis of mRNA expression levels for 37 genes selected from a normal rat hippocampus cDNA library. mRNA amounts were quantified using a Real Time PCR SYBR Green assay. We found that, in general, individuals from an inbred rat population (n = 20) have shown 2-3 times differences in the basal level of expression of the genes analyzed. Up to several fold differences among individuals were observed for certain genes. These inter-individual differences were obtained after correction for the different amounts of mRNA in each sample. Power calculations were performed to determine the number of individuals required to detect reliable differences in expression levels between a control and an experimental group. These data indicated that, depending on the variability of the candidate gene selected, it was necessary to analyze from five to 135 individuals in each group to detect differences of 50% in the levels of mRNA expression between two groups investigated. The comparison of mRNA abundance from different genes revealed a wide range of expression levels for the 37 genes, showing a 26,000-fold difference between the highest and lowest expressed gene.

Editing of the serotonin 2C receptor pre-mRNA: Effects of the Morris Water Maze

“…This is perhaps not surprising, given the observations of inter-individual variation in other molecular parameters (e.g. mRNA levels among inbred rats (Alfonso et al 2002)). Low editing is, however, relatively rare, because of the 42 mice analyzed in the whole brain experiments, only a single animal showed low levels (Table 3).…”

Attenuation of high sweet solution preference by mood stabilizers: A possible mouse model for the increased reward-seeking domain of mania

“…The data demonstrate that BS mice have a high baseline preference for saccharin solution (face validity) and that this preference is reduced following treatment with the mood stabilizers lithium and valproate but is not affected by the administration of the antidepressant imipramine (predictive validity). Given that high preference for sweet solution was associated with other mania-related behaviors [e.g., increased susceptibility for cocaine and impulsive behaviors (Perry et al, 2007)] and with a number of mechanisms involved in BPD [e.g., the dopaminergic (Muscat and Willner, 1989) and the glutamatergic systems (Alfonso et al, 2002;Duncko et al, 2003)], it is proposed that the model might also possess some initial construct validity.…”

Chronic lithium treatment of B lymphoblasts from bipolar disorder patients reduces transient receptor potential channel 3 levels

“…While it is tempting to speculate that the latter observations imply that the mechanism(s) underlying the effect of Li treatment involves factors regulating the disposition and clearance of the TRPC3 protein at the post-translational level, the large variance in the mRNA measures (up to 6-fold) in the comparison groups, which likely reflects intersubject and natural genetic variations in the gene expression, [32][33][34] may have obscured changes in mRNA levels. That said, the variance of the mean differences for the within-subject Li treatment effect was considerably smaller (CV ¼ 160%) than that for the between-subject comparisons (range of CVs ¼ 210-585%).…”