Unraveling the Role of Astrocytes in Subthalamic Nucleus Deep Brain Stimulation in a Parkinson's Disease Rat Model

Author(s)

Pinheiro Campos, Ana Carolina ^[1] ; Kikuchi, Daniel Seicho ^[2] ; Nardini Paschoa, Amanda Faure ^[1] ; Kuroki, Mayra Akemi ^[1] ; Fonoff, Erich Talamoni ^[3] ; Hamani, Clement ^[4] ; Pagano, Rosana Lima ^[1] ; Hernandes, Marina Sorrentino ^[2]

Affiliation

^[1] Hosp Sirio Libanes, Div Neurosci, BR-01308060 Sao Paulo, SP - Brazil

^[2] Emory Univ, Dept Med, Atlanta, GA 30322 - USA

^[3] Univ Sao Paulo, Dept Neurol, Div Neurosurg, Med Sch, BR-01246903 Sao Paulo - Brazil

^[4] Harquail Ctr Neuromodulat, Sunnybrook Hlth Res Inst, Toronto, ON M4N 3M5 - Canada

• Document type: Journal article
• Source: Cellular and Molecular Neurobiology; v. 40, n. 6, p. 939-954, AUG 2020.
• Web of Science Citations: 1

Abstract

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapeutic strategy for motor symptoms of Parkinson's disease (PD) when L-DOPA therapy induces disabling side effects. Classical inflammatory activation of glial cells is well established in PD, contributing to the progressive neurodegenerative state; however, the role of DBS in regulating the inflammatory response remains largely unknown. To understand the involvement of astrocytes in the mechanisms of action of DBS, we evaluated the effect of STN-DBS in regulating motor symptoms, astrocyte reactivity, and cytokine expression in a 6-OHDA-induced PD rat model. To mimic in vivo DBS, we investigate the effect of high-frequency stimulation (HFS) in cultured astrocytes regulating cytokine induction and NF-kappa B activation. We found that STN-DBS improved motor impairment, induced astrocytic hyperplasia, and reversed increased IFN-gamma and IL-10 levels in the globus pallidus (GP) of lesioned rats. Moreover, HFS activated astrocytes and prevented TNF-alpha-induced increase of monocyte chemoattractant protein-1 (MCP-1) and NF-kappa B activation in vitro. Our results indicate that DBS/HFS may act as a regulator of the inflammatory response in PD states, attenuating classical activation of astrocytes and cytokine induction, potentially through its ability to regulate NF-kappa B activation. These findings may help us understand the role of astrocyte signaling in HFS, highlighting its possible relationship with the effectiveness of DBS in neurodegenerative disorders. (AU)

• FAPESP's process: 17/14020-4 - Evaluation of high frequency stimulation in the astrocytic response in vitro
• Grantee: Ana Carolina Pinheiro Campos
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• 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