Zonisamide reduces nigrostriatal dopaminergic neurodegeneration in a mouse genetic model of Parkinson's disease

Hiromi Sano; Miho Murata; Atsushi Nambu

doi:10.1111/jnc.13116

journal article May 08, 2015

Zonisamide reduces nigrostriatal dopaminergic neurodegeneration in a mouse genetic model of Parkinson's disease

Hiromi Sano Miho Murata Atsushi Nambu

Journal of Neurochemistry Vol. 134 No. 2 pp. 371-381 · Wiley

View at Publisher Save 10.1111/jnc.13116

Abstract

AbstractParkinson'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.
image
Zonisamide (ZNS), an antiepileptic drug, has therapeutic benefits for Parkinson's disease. Chronic ZNS administration improved the survival of dopaminergic neurons and motor function in a genetic mouse model of Parkinson's disease, and increased brain‐derived neurotrophic factor (BDNF) in the brain. ZNS reduces dopaminergic cell death probably through BDNF signaling and may have similar beneficial effects in human parkinsonian patients.

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Metrics

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Citations

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References

Details

Published: May 08, 2015
Vol/Issue: 134(2)
Pages: 371-381
License: View

Authors

H

Hiromi Sano

Division of System Neurophysiology National Institute for Physiological Sciences Okazaki Aichi Japan; Department of Physiological Sciences SOKENDAI (The Graduate University for Advanced Studies) Okazaki Aichi Japan

M

Miho Murata

Department of Neurology National Center Hospital National Center of Neurology and Psychiatry Kodaira Tokyo Japan

A

Atsushi Nambu

Division of System Neurophysiology National Institute for Physiological Sciences Okazaki Aichi Japan; Department of Physiological Sciences SOKENDAI (The Graduate University for Advanced Studies) Okazaki Aichi Japan

Funding

CREST

Sumitomo Dainippon Pharma Co., Ltd.

Nihon Medi-physics Co., Ltd

Cite This Article

Hiromi Sano, Miho Murata, Atsushi Nambu (2015). Zonisamide reduces nigrostriatal dopaminergic neurodegeneration in a mouse genetic model of Parkinson's disease. Journal of Neurochemistry, 134(2), 371-381. https://doi.org/10.1111/jnc.13116

Zonisamide reduces nigrostriatal dopaminergic neurodegeneration in a mouse genetic model of Parkinson's disease

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