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

• Type of Material: Article
• Authors: Ana Carolina Pinheiro Campos, Hospital Sírio-Libanês; Daniel Seicho Kikuchi, Emory University; Amanda Faure Nardini Paschoa, Hospital Sírio-Libanês; Mayra Akemi Kuroki, Hospital Sírio-Libanês; Erich T. Fonoff, Hospital Sírio-Libanês; Clement Hamani, Harquail Centre for Neuromodulation; Rosana Lima Pagano, Hospital Sírio-Libanês; Marina Sorrentino Hernandes, Emory University
• Language: English
• Date: 2020-08-01
• Publisher: Springer/Plenum Publishers
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1007/s10571-019-00784-3
• Title of Journal or Parent Work: Cellular and Molecular Neurobiology
• Volume: 40
• Issue: 6
• Start Page: 939
• End Page: 954
• Grant/Funding Information: This work was supported by the São Paulo Research Foundation (FAPESP: A.C.P.C.—2016/07168–2 and 2017/14020–4), Hospital Sírio-Libanês (R.L.P), and American Heart Association (M.S.H.—17SDG33410777).
• Keywords: Factor alpha; Interferon gamma; High-frequency stimulation; Neurosciences & Neurology; Neurosciences; NF-KAPPA-B; Growth factors; Cell Biology; High frequency stimulation; Astrocytes; Inflammation; Tumor necrosis factor; NF-kappa B; Inflammatory process; Life Sciences & Biomedicine; Quality of life; Sleep oscillations; Science & Technology; Deep brain stimulation; Parkinson's disease; Cytokines
• Research Categories: Biology, Cell; Biology, Neuroscience; Psychology, Psychobiology; Health Sciences, Medicine and Surgery

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-κB activation. We found that STN-DBS improved motor impairment, induced astrocytic hyperplasia, and reversed increased IFN-γ and IL-10 levels in the globus pallidus (GP) of lesioned rats. Moreover, HFS activated astrocytes and prevented TNF-α-induced increase of monocyte chemoattractant protein-1 (MCP-1) and NF-κB 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-κB 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.