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Titolo:
Characterization of acute neurotoxic effects of trimethylolpropane phosphate via neuronal network biosensors
Autore:
Keefer, EW; Gramowski, A; Stenger, DA; Pancrazio, JJ; Gross, GW;
Indirizzi:
Univ N Texas, Dept Biol Sci, UNT Stn, Denton, TX 76203 USA Univ N Texas Denton TX USA 76203 Biol Sci, UNT Stn, Denton, TX 76203 USA Univ N Texas, Ctr Network Neurosci, UNT Stn, Denton, TX 76203 USA Univ N Texas Denton TX USA 76203 Neurosci, UNT Stn, Denton, TX 76203 USA Univ Rostock, Inst Cell Technol, D-18055 Rostock, Germany Univ Rostock Rostock Germany D-18055 l Technol, D-18055 Rostock, Germany USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA USN Washington DC USA 20375 r Biomol Sci & Engn, Washington, DC 20375 USA
Titolo Testata:
BIOSENSORS & BIOELECTRONICS
fascicolo: 7-8, volume: 16, anno: 2001,
pagine: 513 - 525
SICI:
0956-5663(200109)16:7-8<513:COANEO>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
BICYCLIC PHOSPHORUS ESTERS; RAT HIPPOCAMPUS; MICROELECTRODE ARRAYS; INHIBITION; TOXICITY; PATTERNS; CULTURES; RELEASE;
Keywords:
trimethylolpropane phosphate; neuronal network; neurotoxicants;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Agriculture,Biology & Environmental Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Gross, GW Univ N Texas, Dept Biol Sci, UNT Stn, POB 304220, Denton, TX 76203 USA Univ N Texas POB 304220 Denton TX USA 76203 Denton, TX 76203 USA
Citazione:
E.W. Keefer et al., "Characterization of acute neurotoxic effects of trimethylolpropane phosphate via neuronal network biosensors", BIOSENS BIO, 16(7-8), 2001, pp. 513-525

Abstract

We have utilized cultured neuronal networks grown on microelectrode arraysto demonstrate rapid, reliable detection of a toxic compound, trimethylolpropane phosphate (TMPP). Initial experiments. which were performed blind. demonstrated rapid classification of the compound as a convulsant. a findingconsistent with previous whole animal neurobehavioral studies. TMPP (2-200muM) reorganized network spike activity into synchronous, quasi-periodic burst episodes. Integrated burst amplitudes invariably increased, reflectinghigher spike frequencies within each burst. The variability of network burst parameters, quantified as coefficients of variation (CVs), was decreased. Mean CVs for burst duration, interburst interval, and burst rate were lowered by 42 +/- 13, 58 +/- 5.5, and 62 +/- 1.8%, respectively (mean SEM, n =8 cultures, 197 channels). These changes in network activity paralleled the effects induced by bicuculline, a known disinhibitory and seizure-inducing drug, and confirmed classification of TMPP as a potential epileptogenic compound. Simple pharmacological tests permit exploration of mechanisms underlying observed activity shifts. The EC50 for GABA inhibition of network activity was increased from 2.8 to 7.0 muM by 20 muM TMPP and to 20.5 muM by 200 muM TMPP. Parallel dose-response curves suggest that TMPP acts by a competitive antagonism of GABA inhibition, and are consistent with reported patch-clamp analysis of TMPP-induced reduction of inhibitory postsynaptic current amplitudes. The potency of TMPP in generating epileptiform activity invitro was comparable to concentrations reported for in vivo studies. TMPP and bicuculline produced both increases and decreases in burst rate depending on native spontaneous bursting levels. These results demonstrate a need for multivariate analysis of network activity changes to yield accurate predictions of compound effects. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 09:32:29