Gene Chromosomal Organization and Expression in Cultured Human Neurons Exposed to Cocaine and HIV-1 proteins gp120 and tat: Drug Abuse and NeuroAIDS

Abstract

As a model for Neuropsychiatric dysfunction in NeuroAIDS due to HIV-1 infection and drug abuse, we analyzed gene expression in human neurons treated with cocaine and HIV-1 proteins tat and envelope (env). One-way ANOVA showed statistically significant genes among the treatment groups (p < or = 0.0005). The identified genes were then subjected to a "stepwise" analysis using a repeated measures ANOVA to discover genes with parallel response group profiles across the treatment conditions. These groups were then analyzed using a repeated measures ANOVA to assess treatment main effects and gene-by-treatment interactions within groups. One-way ANOVA produced 35 genes that were significantly associated across all treatment conditions. Factorial analysis of each gene found statistically significant differences: 30--tat, 17--cocaine, 10--env, 6--tat/env, 6--coc/env, and 4--coc/tat. Analyses across genes found three sets of four genes, one set of three genes, and three sets of two genes with parallel profiles. Identified genes had functions included signaling, immune related, and transcription control. The genes were not stochastically arranged on the chromosomes, were in proximity to each other, and to other genes involved in neuropsychiatric diseases. We hypothesize that these genes fall in transcriptionally isolated groups and that abused drugs and HIV-1 proteins trigger transcription overload, coerced expression that may result in damage to the chromosome's control and organization of chromatin transcription machinery.

Bioinformatics models in drug abuse and Neuro-AIDS: Using and developing databases

“…[5–11–12] The Affymetrix HGU95A oligonucleotide chip was used to measure the expression of 12,565 probes. The data were analyzed using a one-way ANOVA (analysis of variance) among the eight treatment groups across genes (p < 0.0005).…”

“…The expression of 35 genes was statistically significant. [5] We then used Pathways Assist (Stratagene, Inc.) to portray pathways among genes through common and divergent relationships. We modeled the neurological processes involved in Drug Abuse and Neuro-AIDS by computational simulation of physiological processes using experimentally derived information.…”

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“…Briefly, gene expression was analyzed in cultured human neurons treated with cocaine and HIV-1 proteins Tat and envelope (Env) [33]. This serves as a model for Neuropsychiatric disease including Dementia in NeuroAIDS due to HIV-1 infection compounded by drug abuse.…”

Gene expression for HIV-associated dementia and HIV encephalitis in microdissected neurons 1: preliminary analysis

“…Functions of these genes included signaling, immune-related functioning, and transcription control. 25 Human brain cortex middle frontal gyrus gene expression profiles were compared for cases of HAD or milder cognitive dysfunction versus HIV-negative cases. This work focused on neuronal dysfunction and possible relationships with subcortical dementia.…”