Subthalamic nucleus deep brain stimulation is neuroprotective in the A53T α-synuclein Parkinson's disease rat model.
Ann Neurol
; 81(6): 825-836, 2017 Jun.
Article
em En
| MEDLINE
| ID: mdl-28470693
ABSTRACT
OBJECTIVE:
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a highly effective symptomatic therapy for motor deficits in Parkinson's disease (PD). An additional, disease-modifying effect has been suspected from studies in toxin-based PD animal models, but these models do not reflect the molecular pathology and progressive nature of PD that would be required to evaluate a disease-modifying action. Defining a disease-modifying effect could radically change the way in which DBS is used in PD.METHODS:
We applied STN-DBS in an adeno-associated virus (AAV) 1/2-driven human mutated A53T α-synuclein (aSyn)-overexpressing PD rat model (AAV1/2-A53T-aSyn). Rats were injected unilaterally, in the substantia nigra (SN), with AAV1/2-A53T-aSyn or control vector. Three weeks later, after behavioral and nigrostriatal dopaminergic deficits had developed, rats underwent STN-DBS electrode implantation ipsilateral to the vector-injected SN. Stimulation lasted for 3 weeks. Control groups remained OFF stimulation. Animals were sacrificed at 6 weeks.RESULTS:
Motor performance in the single pellet reaching task was impaired in the AAV1/2-A53T-aSyn-injected stim-OFF group, 6 weeks after AAV1/2-A53T-aSyn injection, compared to preoperative levels (-82%; p < 0.01). Deficits were reversed in AAV1/2-A53T-aSyn, stim-ON rats after 3 weeks of active stimulation, compared to the AAV1/2-A53T-aSyn stim-OFF rats (an increase of â¼400%; p < 0.05), demonstrating a beneficial effect of DBS. This motor improvement was maintained when the stimulation was turned off and was accompanied by a higher number of tyrosine hydroxylase+ SN neurons (increase of â¼29%), compared to AAV1/2-A53T-aSyn stim-OFF rats (p < 0.05).INTERPRETATION:
Our data support the putative neuroprotective and disease-modifying effect of STN-DBS in a mechanistically relevant model of PD. Ann Neurol 2017;81825-836.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Núcleo Subtalâmico
/
Estimulação Encefálica Profunda
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Alfa-Sinucleína
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Alemanha