Skip Navigation

Publication Detail

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

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

Published In Exp Neurol, (2018 10)

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 parkinsonian symptoms through inhibition of MAO-B, zonisamide may have disease modifying potential through the inhibition of Nav 1.6 and neuroinflammation.

PubMed ID: 30017881 Exiting the NIEHS site

MeSH Terms: Aged; Animals; Antiparkinson Agents/pharmacology*; Female; Humans; Inflammation/metabolism; Male; Mice; Mice, Inbred C57BL; Microglia/drug effects; Microglia/metabolism*; NAV1.6 Voltage-Gated Sodium Channel/biosynthesis*; Neuroprotective Agents/pharmacology; Parkinsonian Disorders/metabolism*; Parkinsonian Disorders/pathology; Zonisamide/pharmacology*

Back
to Top