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

Title

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

Creator

Hossain Muhammad M; Weig Blair; Reuhl Kenneth; Gearing Marla; Wu Long-Jun; Richardson Jason R

Publisher

Experimental neurology

Date

2018
2018-10

Description

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 (20mg/kg, i.p. every 4hx3) following a single injection of MPTP (12.5mg/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-alpha and gp91(phox), 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 parkinsonian symptoms through inhibition of MAO-B, zonisamide may have disease modifying potential through the inhibition of Nav 1.6 and neuroinflammation.

Subject

*gp91(phox); *Microglia; *MPTP; *Na(v)1.6; *Neuroinflammation; *Parkinson's disease; *TNF-alpha; *Voltage-gated sodium channels; *Zonisamide

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

111–119

Volume

308

Citation

Hossain Muhammad M; Weig Blair; Reuhl Kenneth; Gearing Marla; Wu Long-Jun; Richardson Jason R, “The anti-parkinsonian drug zonisamide reduces neuroinflammation: Role of microglial Nav 1.6.,” NEOMED Bibliography Database, accessed March 4, 2021, https://neomed.omeka.net/items/show/3564.

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