Gene Expression in Human brain and Cultured Human Neurons Exposed to cocaine and HIV-1 proteins gpl20 and tat

摘要

Background We studied gene expression in human neurons treated with cocaine, a major drug of abuse worldwide and HTV-1 proteins tat and envelope. We also investigated the differences between gene expression in human brain tissue of HTV+ and HTV- subjects. Our studies are part of several ongoing approaches to the study of NeuroAIDS including directly studying patients, post-mortem tissue, animal models, and cell models. Goals Our goal is to determine the optimum methods to analyze gene expression from cultured human neurons and brain tissue and to suggest genes that may be involved in pathogenesis. Methods We treated cultured neurons with tat, env, and cocaine in a 2x2x2 study design using eight separate conditions. RNA was purified, labeled, and analyzed on Aflymetrix U96A Microarray chips. Data was examined and final results were released that fulfilled Afrymetrix program quality control testing. We then analyzed the resulting intensities using Spotfire and SAS. We employed the Significance analysis of Microarrays (SAM) method to identify differentially expressed genes and to control the false discovery rate (FDR). Results We found different analytic approaches resulted in different genes that distinguishing among the various treatments as detailed in the text. Discussion We find that several methods identify possible diagnostic genes involved in the pathogenesis of NeuroAIDS dementia. They should be compared prior to settling on a primary method. Conclusion We intend to explore further the significance of our findings in order to determine optimum Bioinformatics methods.