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

Author(s)

Pinheiro Campos, Ana Carolina ; Ruiz Martinez, Raquel Chacon ; Vatti Auada, Aline Vivian ; Lebrun, Ivo ; Fonoff, Erich Talamoni ; Hamani, Clement ; Pagano, Rosana Lima

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 20, p. 17-pg., 2022-10-01.

Abstract

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. (AU)

• FAPESP's process: 16/07168-2 - Deep brain stimulation and Parkinson's disease: Control of the neuroinflammation as a therapeutic target
• Grantee: Ana Carolina Pinheiro Campos
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 18/18695-9 - Deep brain stimulation and Parkinsons Disease: neuroinflammation control as therapeutic target
• Grantee: Ana Carolina Pinheiro Campos
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 19/13781-7 - Translational analysis of the therapeutic mechanisms of deep brain stimulation in Parkinson's Disease
• Grantee: Rosana de Lima Pagano
• Support Opportunities: Regular Research Grants