Spinal cord stimulation improves forelimb use in an alpha-synuclein animal model of Parkinson's disease

Abstract

Neuromodulation by spinal cord stimulation has been proposed as a symptomatic treatment for Parkinson's disease. We tested the chronic effects of spinal cord stimulation in a progressive model of Parkinson's based on overexpression of alpha-synuclein in the substantia nigra. Adult Sprague Dawley rats received unilateral injections of adeno-associated virus serotype 6 (AAV6) in the substantia nigra to express alpha-synuclein. Locomotion and forepaw use of the rats were evaluated during the next 10 weeks. Starting on week 6, a group of AAV6-injected rats received spinal cord stimulation once a week. At the end of the experiment, tyrosine hydroxylase and alpha-synuclein immunostaining were performed. Rats with unilateral alpha-synuclein expression showed a significant decrease in the use of the contralateral forepaw, which was mildly but significantly reverted by spinal cord stimulation applied once a week from the 6th to the 10th week after the AAV6 injection. Long-term spinal cord stimulation proved to be effective to suppress or delay motor symptoms in a sustained and progressive model of Parkinson's and might become an alternative, less invasive neuromodulation option to treat this disease.

KEYWORDS:

• Parkinson's disease
• alpha-synuclein
• spinal cord stimulation

Acknowledgements

The authors would like to thank Jessica Nunes for outstanding aid with experimental procedures, Denis Matrov for the alpha-synuclein immunostaining, and the Brain Institute of UFRN for the use of microscopes to generate the alpha-synuclein immunostaining image.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

I. Brys received a doctorate fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). This project was funded by the Swiss Brazilian Scientific & Technology Cooperation, Financiadora de Estudos e Projetos [grant number 01.06.1092.00]; the Instituto Nacional de Interface Cérebro-Máquina [grant number 704134/2009]; partially funded by Núcleo Milenio de Biología de Enfermedades Neuropsiquiátricas [grant number NC 130011].

Additional information

Funding

Instituto Nacional de Interface Cérebro-Máquina [grant number 704134/2009]; partially funded by Núcleo Milenio de Biología de Enfermedades Neuropsiquiátricas [grant number NC 130011].