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Zonisamide reduces nigrostriatal dopaminergic neurodegeneration in a mouse genetic model of Parkinson's disease.
Sano, Hiromi; Murata, Miho; Nambu, Atsushi.
Afiliação
  • Sano H; Division of System Neurophysiology, National Institute for Physiological Sciences, Okazaki, Aichi, Japan.
  • Murata M; Department of Physiological Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi, Japan.
  • Nambu A; Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
J Neurochem ; 134(2): 371-81, 2015 Jul.
Article em En | MEDLINE | ID: mdl-25857446
Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the loss of nigrostriatal dopaminergic neurons and consequent motor dysfunction. Zonisamide (1,2-benzisoxazole-3-methanesulfonamide), which was originally developed as an antiepileptic drug, has been found to have therapeutic benefits for PD. However, the pharmacological mechanisms behind the beneficial actions of zonisamide in PD are not fully understood. Here, we investigated the neuroprotective effects of zonisamide on nigrostriatal dopaminergic neurons of the Engrailed mutant mouse, a genetic model of PD. Chronic administration of zonisamide in Engrailed mutant mice was shown to improve the survival of nigrostriatal dopaminergic neurons compared with that under saline treatment. In addition, dopaminergic terminals in the striatum and the motor function were improved in zonisamide-treated Engrailed mutant mice to the levels of those in control mice. To clarify the mechanism behind the neuroprotective effects of zonisamide, the contents of neurotrophic factors were determined after chronic administration of zonisamide. Brain-derived neurotrophic factor content was increased in the striatum and ventral midbrain of the zonisamide-treated mice compared to saline-treated mice. These findings imply that zonisamide reduces nigrostriatal dopaminergic cell death through brain-derived neurotrophic factor signaling and may have similar beneficial effects in human parkinsonian patients as well.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Fármacos Neuroprotetores / Transtornos Parkinsonianos / Neurônios Dopaminérgicos / Isoxazóis / Degeneração Neural Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Fármacos Neuroprotetores / Transtornos Parkinsonianos / Neurônios Dopaminérgicos / Isoxazóis / Degeneração Neural Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2015 Tipo de documento: Article