title: 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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Miami School of Medicine, Miami, FL 33136, USA. pshapsha@med.miami.edu
authors.forename: Paul
authors.initials: P
authors.lastname: Shapshak
authors.forename: Robert
authors.initials: R
authors.lastname: Duncan
authors.forename: Avindra
authors.initials: A
authors.lastname: Nath
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Turchan
authors.forename: Kangueane
authors.initials: K
authors.lastname: Pandjassarame
authors.forename: Hector
authors.initials: H
authors.lastname: Rodriguez
authors.forename: Elda Margarita
authors.initials: EM
authors.lastname: Duran
authors.forename: Fabiana
authors.initials: F
authors.lastname: Ziegler
authors.forename: Eric
authors.initials: E
authors.lastname: Amaro
authors.forename: Apple
authors.initials: A
authors.lastname: Lewis
authors.forename: Alejandro
authors.initials: A
authors.lastname: Rodriguez
authors.forename: Alireza
authors.initials: A
authors.lastname: Minagar
authors.forename: Wade
authors.initials: W
authors.lastname: Davis
authors.forename: Raman
authors.initials: R
authors.lastname: Seth
authors.forename: Fatten F
authors.initials: FF
authors.lastname: Elkomy
authors.forename: Francesco
authors.initials: F
authors.lastname: Chiappelli
authors.forename: Toni
authors.initials: T
authors.lastname: Kazic
mesh_terms: D015526:AIDS Dementia Complex / Q000473:pathology; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000473:pathology; D000704:Analysis of Variance; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002875:Chromosomes / Q000648:ultrastructure*; D003042:Cocaine / Q000494:pharmacology*; D019295:Computational Biology / Q000379:methods; D004660:Encephalitis / Q000378:metabolism; D005786:Gene Expression Regulation; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D008954:Models, Biological; D015233:Models, Statistical; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D015699:HIV Envelope Protein gp120; D003042:Cocaine