GIRARDI Elena Silvia
congresos y reuniones científicas
Neuronal MDR-1 gene encoded P-glycoprotein (P-170) expresión in 3-mercaptopropionic acid induced seizures in rats?
Washington Seattle
Encuentro; Annual Meeting of the American Epilepsy Society. Seattle. Washington; 2002
1024 NEURONAL MDR-1 GENE?ENCODED P-GLYCOPROTEIN (P-170) EXPRESSION IN 3-MERCAPTOPROPIONIC ACID? INDUCED SEIZURES IN RATS Alberto J. Lazarowski, Elena Girardi, Javier A. Ramos, Hernan Garcia- Rivelo, and Alicia Brusco (Bioquimica Clinica, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Buenos Aires, Argentina; Instituto de Biologia Celular y Neurobiología Prof. Dr. Eduardo de Robertis, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina; Anatomía Patológica, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina) Rationale: MDR-1 gene?encoded P-glycoprotein (P-170) is involved in the multiple drug resistance mechanism observed in cancer, and it was recently described to be expressed in brain of patients with refractory epilepsy (Tishler, 1995; Lazarowski, 1999; Sisodiya, 2002). We previously demonstrated that the expression of P-170 was induced after 4 days of treatment with i.p. administered proconvulsivant drug 3-mercaptopropionic acid (MP), in brain vessel walls, astrocytes, foot process astrocytes, and lightly in surrounding neurons (Lazarowski et al., 2002) The aim of this study was to analyze whether longer times of MP treatment can induce a greater P-170 expression in neurons. Methods: Male Wistar rats (250?300 g) were daily administered 45 mg/kg i.p. of MP during 4 days (MP-4) and 7 days (MP-7). Rats daily injected with saline were used as controls. One day after the last injection, rats were deeply anesthetized with chloral hydrate (300 mg/kg) and fixed by perfusion. Brains were dissected and processed for immunohistochemistry by using monoclonal anti-P170 as primary antibody and the peroxidase?antiperoxidase technique. Results: Brain sections of MP- 4?treated animals showed intense P-170 expression in striatum and cerebral cortex. Immunoreactivity was prominent in the capillary endothelium and surrounding astrocytes, and also evident although less intense in a few neuron fibers. In MP-7, extensive neuronal areas were stained in the same brain regions, and the imges showed sparse immunostaining on neurons, increasing highly the intensity near the vessels. In control animals, P-170 expression was minimal, showing a light and sparse labeling on a few blood vessels. Conclusions: These results showed a differential pattern of expression of MDR-1 gene (P-170) in brain MP-treated rats in 4 and 7 days. A longer time of MP treatment induced more extensive neuronal MDR-1 gene expression. It is the first experimental model of MDR-1 gene neuronal expression induced by proconvulsivant drug treatment. [Supported by University of Buenos Aires (UBACYT B-033), CONICET and Ministerio de Salud, Argentina.] (Disclosure: Grant: UBACYT B33, CONICET, and Ministerio de Salud, Argentina.) AES PROCEEDINGS 11 Epilepsia, Vol. 43, Suppl. 7, 2002 Epilepsia, 43(Suppl. 7):1?351, 2002 Blackwell Publishing, Inc. © International League Against Epilepsy AES Proceedings Annual Meeting of the American Epilepsy Society Seattle, Washington, December 6?11, 2002