title: Changes in extracellular action potential detect kainic acid and trimethyltin toxicity in hippocampal slice preparations earlier than do MAP2 density measurements.
abstract: In vitro electrophysiological techniques for the assessment of neurotoxicity could have several advantages over other methods in current use, including the ability to detect damage at a very early stage, and could further assist in replacing animal experimentation in vivo. We investigated how an electrophysiological parameter, the extracellularly-recorded compound action potential ("population spike", PS) could be used as a marker of in vitro neurotoxicity in the case of two well-known toxic compounds, kainic acid (KA) and trimethyltin (TMT). We compared the use of this electrophysiological endpoint with changes in immunoreactivity for microtubule-associated protein 2 (MAP2), a standard histological test for neurotoxicity. We found that both toxic compounds reliably caused disappearance of the PS, and that such disappearance occurred after only 1 hour of exposure to the drug. By contrast, densitometric measurements of MAP2 immunoreactivity were unaffected by both KA and TMT after such a short exposure time. We conclude that, in the case of KA and TMT, the extracellular PS was abolished at a very early time-point, when MAP2 immunoreactivity levels were still comparable to those of the untreated controls. Electrophysiology could be a reliable and early indicator of neurotoxicity, which could improve our ability to test for neurotoxicity in vitro, thus further replacing the need for in vivo experimentation.
authors.affiliation: Department of Neuroscience, Ophthalmology and Genetics, University of Genoa, Via De Toni 5, 16132 Genoa, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Melani
authors.forename: Reneta
authors.initials: R
authors.lastname: Rebaudo
authors.forename: Jens
authors.initials: J
authors.lastname: Noraberg
authors.forename: Jens
authors.initials: J
authors.lastname: Zimmer
authors.forename: Maurizio
authors.initials: M
authors.lastname: Balestrino
mesh_terms: D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007608:Kainic Acid / Q000633:toxicity*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D013997:Time Factors; D014298:Trimethyltin Compounds / Q000633:toxicity*
chemical_list: D018690:Excitatory Amino Acid Agonists; D008869:Microtubule-Associated Proteins; D014298:Trimethyltin Compounds; C046488:trimethyltin; D007608:Kainic Acid