Author: Ariana Farran, Ryan Verner, Ryan McGuire, Kristi Helke, Vanessa Hinson, Heather Boger
Affiliation: <sup>1</sup> Department of Neuroscience and Center on Aging, Medical University of South Carolina, 173 Ashley Ave, BSB Suite 403, MSC 510, Charleston, SC, 29425, USA.
<sup>2</sup> Neuromodulation Division of LivaNova, PLC, 100 Cyberonics Blvd, Houston, TX, 77058, USA.
<sup>3</sup> Department of Comparative Medicine, 114 Doughty St, STB 648, MSC 777, and Department of Pathology and Laboratory Medicine, 165 Ashely Ave, Children's Hospital 309, MSC 908, Medical University of South Carolina, Charleston, SC, 29425, USA.
<sup>4</sup> Department of Neurology, Medical University of South Carolina, 96 Jonathan Lucas St, CSB 309, MSC 606, Charleston, SC, 29425, USA.
<sup>5</sup> Department of Neuroscience and Center on Aging, Medical University of South Carolina, 173 Ashley Ave, BSB Suite 403, MSC 510, Charleston, SC, 29425, USA. Electronic address: boger@musc.edu.
Conference/Journal: Brain Stimul
Date published: 2020 Jul 3
Other:
Pages: S1935-861X(20)30196-0 , Special Notes: doi: 10.1016/j.brs.2020.06.078. , Word Count: 267
PMID: 32629028 DOI: 10.1016/j.brs.2020.06.078
Abstract
Background: Vagus nerve stimulation (VNS) modifies brain rhythms in the locus coeruleus (LC) via the solitary nucleus. Degeneration of the LC in Parkinson's disease (PD) is an early catalyst of the spreading neurodegenerative process, suggesting that stimulating LC output with VNS has the potential to modify disease progression. We previously showed in a lesion PD model that VNS delivered twice daily reduced neuroinflammation and motor deficits, and attenuated TH-positive cell loss.
Objective: The goal of this study was to characterize the differential effects of three clinically-relevant VNS paradigms in a PD lesion model.
Methods: Eleven days after DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, noradrenergic lesion, administered systemically)/6-OHDA (6-hydroxydopamine, dopaminergic lesion, administered intrastriatally) rats were implanted with VNS devices, and rats received either low-frequency VNS, standard-frequency VNS, or high-frequency microburst VNS. After 10 days of treatment and behavioral assessment, rats were euthanized, right prefrontal cortex (PFC) was dissected for norepinephrine assessment, and the left striatum, bilateral substantia nigra (SN), and LC were sectioned for immunohistochemical detection of catecholamine neurons, α-synuclein, astrocytes, and microglia.
Results: At higher VNS frequencies, specifically microburst VNS, greater improvements occurred in motor function, attenuation of TH-positive cell loss in SN and LC, and norepinephrine concentration in the PFC. Additionally, higher VNS frequencies resulted in lower intrasomal α-synuclein accumulation and glial density in the SN.
Conclusions: These data indicate that higher stimulation frequencies provided the greatest attenuation of behavioral and pathological markers in this PD model, indicating therapeutic potential for these VNS paradigms.
Keywords: Parkinson’s disease; dopamine; locus coeruleus; nigrostriatal system; norepinephrine; vagus nerve stimulation.
Copyright © 2020. Published by Elsevier Inc.