The anti-parkinsonian drug zonisamide reduces neuroinflammation: Role of microglial Nav 1.6

Experimental Neurology
Muhammad M HossainJason R Richardson

Abstract

Parkinson's disease (PD), the second most common age-related progressive neurodegenerative disorder, is characterized by dopamine depletion and the loss of dopaminergic (DA) neurons with accompanying neuroinflammation. Zonisamide is an-anti-convulsant drug that has recently been shown to improve clinical symptoms of PD through its inhibition of monoamine oxidase B (MAO-B). However, zonisamide has additional targets, including voltage-gated sodium channels (Nav), which may contribute to its reported neuroprotective role in preclinical models of PD. Here, we report that Nav1.6 is highly expressed in microglia of post-mortem PD brain and of mice treated with the parkinsonism-inducing neurotoxin MPTP. Administration of zonisamide (20 mg/kg, i.p. every 4 h × 3) following a single injection of MPTP (12.5 mg/kg, s.c.) reduced microglial Nav 1.6 and microglial activation in the striatum, as indicated by Iba-1 staining and mRNA expression of F4/80. MPTP increased the levels of the pro-inflammatory cytokine TNF-α and gp91phox, and this was significantly reduced by zonisamide. Together, these findings suggest that zonisamide may reduce neuroinflammation through the down-regulation of microglial Nav 1.6. Thus, in addition to its effects on...Continue Reading

Citations

Aug 6, 2019·Frontiers in Neuroscience·R Dixon DorandAlex Y Huang
Jun 15, 2019·Acta Neuropathologica·Jason R RichardsonAnumantha G Kanthasamy
Dec 6, 2019·Frontiers in Cellular Neuroscience·Cai-Yun LiuHong-Liang Zhang
Aug 28, 2020·International Journal of Molecular Sciences·Huifangjie LiJinbin Xu
Oct 1, 2020·Environmental Science and Pollution Research International·Supriya SharmaFaheem Hyder Pottoo
May 3, 2019·Current Pain and Headache Reports·Omar ViswanathAlan D Kaye
Jan 8, 2021·Frontiers in Neuroscience·Chengqian LiAnmu Xie
Mar 5, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Chen ZhaoHaifeng Liu
Nov 29, 2020·Neurochemistry International·Lanxin LuoDandan Sun
Apr 4, 2021·Journal of Clinical Medicine·Alexandru CojocaruEugen Osiac

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