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

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorCAMPOS, Ana Carolina Pinheiro
dc.contributor.authorMARTINEZ, Raquel Chacon Ruiz
dc.contributor.authorAUADA, Aline Vivian Vatti
dc.contributor.authorLEBRUN, Ivo
dc.contributor.authorFONOFF, Erich Talamoni
dc.contributor.authorHAMANI, Clement
dc.contributor.authorPAGANO, Rosana Lima
dc.date.accessioned2022-12-21T13:23:42Z
dc.date.available2022-12-21T13:23:42Z
dc.date.issued2022
dc.description.abstractDeep 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.eng
dc.description.indexMEDLINEeng
dc.description.sponsorshipSao Paulo Research Foundation [FAPESP: 2016/07168-2, 2018/18695-9, 2019/13781-7]
dc.description.sponsorshipHospital Sirio-Libanes
dc.identifier.citationINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.23, n.20, article ID 12116, 17p, 2022
dc.identifier.doi10.3390/ijms232012116
dc.identifier.eissn1422-0067
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/50572
dc.language.isoeng
dc.publisherMDPIeng
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.rightsopenAccesseng
dc.rights.holderCopyright MDPIeng
dc.subjectParkinson's diseaseeng
dc.subjectdeep brain stimulationeng
dc.subjectsubthalamic stimulationeng
dc.subjectneuroinflammationeng
dc.subjectastrocyteseng
dc.subjectglutamate excitotoxicityeng
dc.subject.otherdeep brain-stimulationeng
dc.subject.otherdopaminergic-neuronseng
dc.subject.otherfocused ultrasoundeng
dc.subject.othersubstantia-nigraeng
dc.subject.otherglutamateeng
dc.subject.othernucleuseng
dc.subject.otherastrocyteseng
dc.subject.othermicrogliaeng
dc.subject.othersynapseseng
dc.subject.otherexcitotoxicityeng
dc.subject.wosBiochemistry & Molecular Biologyeng
dc.subject.wosChemistry, Multidisciplinaryeng
dc.titleEffect of Subthalamic Stimulation and Electrode Implantation in the Striatal Microenvironment in a Parkinson's Disease Rat Modeleng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryCanadá
hcfmusp.affiliation.countryisoca
hcfmusp.author.externalCAMPOS, Ana Carolina Pinheiro:Hosp Sirio Libanes, Lab Neurosci, BR-01308901 Sao Paulo, Brazil
hcfmusp.author.externalAUADA, Aline Vivian Vatti:Butantan Inst, Biochem & Biophys Lab, BR-05508040 Sao Paulo, Brazil
hcfmusp.author.externalLEBRUN, Ivo:Butantan Inst, Biochem & Biophys Lab, BR-05508040 Sao Paulo, Brazil
hcfmusp.author.externalHAMANI, Clement:Sunnybrook Res Inst, Brain Sci Program, Toronto, ON M4N 3M5, Canada
hcfmusp.author.externalPAGANO, Rosana Lima:Hosp Sirio Libanes, Lab Neurosci, BR-01308901 Sao Paulo, Brazil
hcfmusp.citation.scopus6
hcfmusp.contributor.author-fmusphcRAQUEL CHACON RUIZ MARTINEZ
hcfmusp.contributor.author-fmusphcERICH TALAMONI FONOFF
hcfmusp.description.articlenumber12116
hcfmusp.description.issue20
hcfmusp.description.volume23
hcfmusp.origemWOS
hcfmusp.origem.pubmed36292973
hcfmusp.origem.scopus2-s2.0-85141000195
hcfmusp.origem.wosWOS:000873048000001
hcfmusp.publisher.cityBASELeng
hcfmusp.publisher.countrySWITZERLANDeng
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