Artículo
Comparative analyses of the neurodegeneration induced by the non-competitive NMDA-receptor-antagonist drug MK801 in mice and rats
Bender, Crhistian Luis
; de Olmos, Soledad
; Bueno, Adrián Marcelo; de Olmos, Jose Severo Ramon
; Lorenzo, Alfredo Guillermo
Fecha de publicación:
09/2010
Editorial:
Pergamon-Elsevier Science Ltd
Revista:
Neurotoxicology and Teratology
ISSN:
0892-0362
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Non-competitive NMDA-receptor-antagonist drugs such as dizocilpine (MK801) induce behavioral changes and neurotoxicity that have made an impact in different fields of neuroscience. New approaches in research use transgenic mice to elucidate cellular mechanisms and circuits involved in the effects of these drugs. However, the neurodegeneration induced by these drugs has been extensively studied in rats, but the data in mice is limited. Therefore it is important to characterize if the neurotoxic pattern in mice corresponds to that of rats.A comparative analysis of the neurodegeneration induced by MK801 (10. mg/kg) between Wistar rats, and CD-1, CF-1, and C57BL/6-129/Sv mice of both sexes, at different survival times (15, 24, 32, 48, 56 and 72. h) was analysed with the amino-cupric-silver and fluoro-jade B techniques. To compare different administration patterns, groups of mice received subchronic treatments with different doses (final doses of 20 and 40. mg/kg).Results showed that mice treated with MK801 presented different neurotoxic profiles, such as excitotoxic-like cell death in the retrosplenial cortex, terminal degeneration in CA1 and apoptotic-like degeneration in the olfactory bulb. Unlike rats, mice subjected to the same treatment failed to show neurodegeneration in corticolimbic areas such as piriform cortex and dentate gyrus. The amount of degeneration was lower in mice, and the subchronic administration of MK801 did not change the neurotoxic pattern. Additionally, mice lacked the sexually dimorphic response to MK801 toxicity observed in rats. Altogether these results indicate important species dissimilarities. Neurotoxicological studies aimed to explore pathways and mechanisms of MK801 toxicity should consider these differences when using mice as rodent models.
Palabras clave:
ANIMAL MODELS
,
MICE
,
MK801
,
NEURODEGENERATION
,
NON-COMPETITIVE NMDA ANTAGONIST
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Identificadores
Colecciones
Articulos(INIMEC - CONICET)
Articulos de INSTITUTO DE INV. MEDICAS MERCEDES Y MARTIN FERREYRA
Articulos de INSTITUTO DE INV. MEDICAS MERCEDES Y MARTIN FERREYRA
Citación
Bender, Crhistian Luis; de Olmos, Soledad; Bueno, Adrián Marcelo; de Olmos, Jose Severo Ramon; Lorenzo, Alfredo Guillermo; Comparative analyses of the neurodegeneration induced by the non-competitive NMDA-receptor-antagonist drug MK801 in mice and rats; Pergamon-Elsevier Science Ltd; Neurotoxicology and Teratology; 32; 5; 9-2010; 542-550
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