title: Gene modulation in total brain induced by exposure to the bicyclic phosphorus ester trimethylolpropane phosphate (TMPP).
abstract: The effect of a single subconvulsive dose of the GABAergic convulsant trimethylolpropane phosphate (TMPP) on gene expression in total rat brain was examined using cDNA array analysis. Using threshold criteria that reduce the number of false positives to <1 gene per 3551 actively transcribed genes on the cDNA array, 41 genes/EST sequences were reproducibly modulated in response to 0.25 mg/kg TMPP. Several genes that were consistent with epileptogenesis and/or neuronal damage and repair mechanisms, such as trkB, alphaB-crystallin, and decorin, were modulated by TMPP exposure in the absence of clinical convulsions. Previous research indicates that rats exposed to subconvulsive doses of TMPP exhibit both "absence-like" EEG paroxysms and persisting central nervous system (CNS) sensitization, as evidenced by increased susceptibility to audiogenic seizures (AGS). Results of this study suggest that cDNA arrays can be used to identify gene modulation events induced by low-level exposure to a chemical convulsant in a reproducible manner.
authors.affiliation: SRIF George Mason University, Fairfax, VA, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Russell
authors.forename: M Y V
authors.initials: MY
authors.lastname: Bekkedal
authors.forename: T T
authors.initials: TT
authors.lastname: Mann
authors.forename: G D
authors.initials: GD
authors.lastname: Ritchie
authors.forename: J
authors.initials: J
authors.lastname: Rossi
authors.forename: D A
authors.initials: DA
authors.lastname: Stenger
authors.forename: J J
authors.initials: JJ
authors.lastname: Pancrazio
authors.forename: J D
authors.initials: JD
authors.lastname: Andreadis
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D004785:Environmental Pollutants; C065518:4-ethyl-1-phospha-2,6,7 trioxabicyclo(2.2.2)octane-1-oxide