Protein tyrosine kinase inhibitors modify kainic acid-induced epileptiform activity and mossy fiber sprouting but do not protect against limbic cell death
Braz. j. med. biol. res
; 41(5): 403-410, May 2008. ilus
Article
em En
| LILACS
| ID: lil-484433
Biblioteca responsável:
BR1.1
ABSTRACT
Intrahippocampal administration of kainic acid (KA) induces synaptic release of neurotrophins, mainly brain-derived neurotrophic factor, which contributes to the acute neuronal excitation produced by the toxin. Two protein tyrosine kinase inhibitors, herbimycin A and K252a, were administered intracerebroventricularly, in a single dose, to attenuate neurotrophin signaling during the acute effects of KA, and their role in epileptogenesis was evaluated in adult, male Wistar rats weighing 250-300 g. The latency for the first Racine stage V seizure was 90 ± 8 min in saline controls (N = 4) which increased to 369 ± 71 and 322 ± 63 min in animals receiving herbimycin A (1.74 nmol, N = 4) and K252a (10 pmol, N = 4), respectively. Behavioral alterations were accompanied by diminished duration of EEG paroxysms in herbimycin A- and K252a-treated animals. Notwithstanding the reduction in seizure severity, cell death (60-90 percent of cell loss in KA-treated animals) in limbic regions was unchanged by herbimycin A and K252a. However, aberrant mossy fiber sprouting was significantly reduced in the ipsilateral dorsal hippocampus of K252a-treated animals. In this model of temporal lobe epilepsy, both protein kinase inhibitors diminished the acute epileptic activity triggered by KA and the ensuing morphological alterations in the dentate gyrus without diminishing cell loss. Our current data indicating that K252a, but not herbimycin, has an influence over KA-induced mossy fiber sprouting further suggest that protein tyrosine kinase receptors are not the only factors which control this plasticity. Further experiments are necessary to elucidate the exact signaling systems associated with this K252a effect.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
LILACS
Assunto principal:
Proteínas Tirosina Quinases
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Carbazóis
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Benzoquinonas
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Fibras Musgosas Hipocampais
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Alcaloides Indólicos
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Lactamas Macrocíclicas
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Epilepsia do Lobo Temporal
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Ácido Caínico
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Braz. j. med. biol. res
Assunto da revista:
BIOLOGIA
/
MEDICINA
Ano de publicação:
2008
Tipo de documento:
Article
/
Project document
País de afiliação:
Brasil
País de publicação:
Brasil