Effect of Subthalamic Stimulation and Electrode Implantation in the Striatal Microenvironment in a Parkinson's Disease Rat Model

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Citações na Scopus
5
Tipo de produção
article
Data de publicação
2022
Título da Revista
ISSN da Revista
Título do Volume
Editora
MDPI
Autores
CAMPOS, Ana Carolina Pinheiro
AUADA, Aline Vivian Vatti
LEBRUN, Ivo
HAMANI, Clement
PAGANO, Rosana Lima
Citação
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.23, n.20, article ID 12116, 17p, 2022
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is considered the gold-standard treatment for PD; however, underlying therapeutic mechanisms need to be comprehensively elucidated, especially in relation to glial cells. We aimed to understand the effects of STN-microlesions and STN-DBS on striatal glial cells, inflammation, and extracellular glutamate/GABAergic concentration in a 6-hydroxydopamine (6-OHDA)-induced PD rat model. Rats with unilateral striatal 6-OHDA and electrodes implanted in the STN were divided into two groups: DBS OFF and DBS ON (5 days/2 h/day). Saline and 6-OHDA animals were used as control. Akinesia, striatal reactivity for astrocytes, microglia, and inflammasome, and expression of cytokines, cell signaling, and excitatory amino acid transporter (EAAT)-2 were examined. Moreover, striatal microdialysis was performed to evaluate glutamate and GABA concentrations. The PD rat model exhibited akinesia, increased inflammation, glutamate release, and decreased glutamatergic clearance in the striatum. STN-DBS (DBS ON) completely abolished akinesia. Both STN-microlesion and STN-DBS decreased striatal cytokine expression and the relative concentration of extracellular glutamate. However, STN-DBS inhibited morphological changes in astrocytes, decreased inflammasome reactivity, and increased EAAT2 expression in the striatum. Collectively, these findings suggest that the beneficial effects of DBS are mediated by a combination of stimulation and local microlesions, both involving the inhibition of glial cell activation, neuroinflammation, and glutamate excitotoxicity.
Palavras-chave
Parkinson's disease, deep brain stimulation, subthalamic stimulation, neuroinflammation, astrocytes, glutamate excitotoxicity
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