Palotás A, Puskás LG, Kitajka K, Palotás M, Molnár J, Pákáski M, Janka Z, Penke B, Kálmán J.
Altered response to mirtazapine on gene expression profile of lymphocytes from Alzheimer's patients.
Eur J Pharmacol. 2004 Aug 30;497(3):247-54.
PubMed.
This interesting paper reports an effect of a novel antidepressant on gene expression profiles of cultured lymphocytes derived from eight AD and eight control patients. To do this they used "homemade" cDNA arrays, representing 3,200 transcripts to analyze gene expression of treated and untreated control and AD lymphocytes. The major body of data reported consists of a list of 20 genes differentially affected by drug treatment of control lymphocytes and 26 genes differentially affected by drug treatment of AD lymphocytes. Comparing these two lists leads authors to conclude that AD and control lymphocytes respond differently to drug (mirtazapine). They validated the results of seven transcripts by real-time quantitative RT-PCR, a positive aspect of this study.
The concept of performing this type of study is excellent. However, there are a number of aspects of methods that are not described. These include the important issue of how lymphocytes were purified from whole blood and times (and storage conditions, if any) between collection, purification, and RNA extraction. In addition, beta actin and GAPDH were used as loading control or normalization transcripts, which is inappropriate since expression of both of these is known to be changed in AD. Samples from four individuals were pooled—one can guess in order to provide a sufficient amount of RNA for analysis. It seems that all data were analyzed by t-test, (the only statistical test of significance mentioned) with significance level set at pThe driving rationale for this work derives from the authors' previous finding that alpha2 adrenoceptor is the most highly repressed transcript in AD and the action of mirtazapine as an alpha2 adrenoceptor antagonist. The transcripts found to be differentially expressed are largely unrelated to this rationale. Nevertheless, their data do lead the authors to refer to AD as a systemic disease—a characterization with which this reviewer agrees, although the data presented here do not formally prove this to be so.
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Banner Research Institute
This interesting paper reports an effect of a novel antidepressant on gene expression profiles of cultured lymphocytes derived from eight AD and eight control patients. To do this they used "homemade" cDNA arrays, representing 3,200 transcripts to analyze gene expression of treated and untreated control and AD lymphocytes. The major body of data reported consists of a list of 20 genes differentially affected by drug treatment of control lymphocytes and 26 genes differentially affected by drug treatment of AD lymphocytes. Comparing these two lists leads authors to conclude that AD and control lymphocytes respond differently to drug (mirtazapine). They validated the results of seven transcripts by real-time quantitative RT-PCR, a positive aspect of this study.
The concept of performing this type of study is excellent. However, there are a number of aspects of methods that are not described. These include the important issue of how lymphocytes were purified from whole blood and times (and storage conditions, if any) between collection, purification, and RNA extraction. In addition, beta actin and GAPDH were used as loading control or normalization transcripts, which is inappropriate since expression of both of these is known to be changed in AD. Samples from four individuals were pooled—one can guess in order to provide a sufficient amount of RNA for analysis. It seems that all data were analyzed by t-test, (the only statistical test of significance mentioned) with significance level set at pThe driving rationale for this work derives from the authors' previous finding that alpha2 adrenoceptor is the most highly repressed transcript in AD and the action of mirtazapine as an alpha2 adrenoceptor antagonist. The transcripts found to be differentially expressed are largely unrelated to this rationale. Nevertheless, their data do lead the authors to refer to AD as a systemic disease—a characterization with which this reviewer agrees, although the data presented here do not formally prove this to be so.
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