Vagus nerve stimulation improves locomotion and neuronal populations in a model of Parkinson's disease

Publication date: Available online 24 August 2017
Source:Brain Stimulation
Author(s): Ariana Q. Farrand, Kristi L. Helke, Rebecca A. Gregory, Monika Gooz, Vanessa K. Hinson, Heather A. Boger
BackgroundParkinson's disease (PD) is a progressive, neurodegenerative disorder with no disease-modifying therapies, and symptomatic treatments are often limited by debilitating side effects. In PD, locus coeruleus (LC) noradrenergic neurons degenerate prior to substantia nigra (SN) dopaminergic neurons. Vagus nerve stimulation (VNS) beneficially alters LC neurons, and decreases pro-inflammatory markers, allowing functional improvement of LC and its targets, making it a potential PD therapeutic.ObjectiveTo assess therapeutic potential of VNS in a PD model.MethodsTo mimic the progression of degeneration associated with PD, rats received a systemic injection of the noradrenergic neurotoxin DSP-4, followed one week later by bilateral intrastriatal injection of the dopaminergic neurotoxin 6-hydroxydopamine. At this time, a subset of rats also had vagus cuffs implanted. After eleven days, rats received a precise VNS regimen twice a day for ten days, and locomotion was measured during the afternoon session daily. Immediately following final stimulation, rats were euthanized, and left dorsal striatum, bilateral SN and LC were sectioned for immunohistochemical detection of monoaminergic neurons (tyrosine hydroxylase, TH), α-synuclein, astrocytes (GFAP) and microglia (Iba-1).ResultsVNS significantly increased locomotion of lesioned rats. It also resulted in increased expression of TH in striatum, SN, and LC; decreased expression of α-synuclein in SN; and decreased expression of glial markers in the SN and LC of lesioned rats. Additionally, after VNS, TH was higher in the LC and Iba-1 lower in the SN of saline-treated rats.ConclusionsThese data suggest that VNS has potential as a novel PD therapeutic.



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