Evaluation of high frequency stimulation in the astrocytic response in vitro

• Grant number: 17/14020-4
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: August 30, 2017
• End date: February 27, 2018
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Rosana de Lima Pagano
• Grantee: Ana Carolina Pinheiro Campos
• Supervisor: Kathy K Griendling
• Host Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil
• Institution abroad: Emory University, United States
• Associated to the scholarship: 16/07168-2 - Deep brain stimulation and Parkinson's disease: Control of the neuroinflammation as a therapeutic target, BP.MS

Abstract

Despite its widespread use, the underlying mechanisms of high frequency stimulation (HFS), as used in deep brain stimulation (DBS) therapy, remain unknown. HFS has been shown to directly modulate astrocyte activation, contributing to HFS beneficial effects. In this context, astrocytes may be considered key players in promoting the wide range of observed HFS therapeutic effects. Reactive astrocytes may have a dual role in neurological diseases, displaying neurotoxic or neuroprotective phenotypes depending on the nature of the immune or inflammatory microenvironments or insults. These phenotypes are defined by its polarization state. While the A1 subtype might be pro-inflammatory, the A2 subtype has been shown to be anti-inflammatory and neuroprotective. Given the importance of understanding the mechanisms of action of HFS to improve therapeutic efficacy, as well as the relevant role of astrocytes in this response, we have decided to address the following question: Can HFS change the astrocytic phenotype from a neurotoxic pro-inflammatory (subtype A1) to a neuroprotective anti-inflammatory phenotype (subtype A2) and consequently reestablish adequate neurophysiological conditions in patients with advanced neurological diseases? To test this hypothesis, we will evaluate the ability of HFS to alter the polarization phenotype of astrocytes in vitro. Astrocytes will be first actived by a TNF-± treatment and then stimulated with HFS at 130 Hz for 1 min. The mRNA expression of cytokines, neurotrophic factors, C3 component complement, as well as the immunofluorescence against the astrocyte marker GFAP, will be evaluated at different time points following the stimulation. Findings from our experiments will generate data on the potential effects of HFS on astrocytic phenotypes and may help us to uncover novel targets for anti-inflammatory drugs.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

KIKUCHI, DANIEL S.; CAMPOS, ANA CAROLINA P.; QU, HONGYAN; FORRESTER, STEVEN J.; PAGANO, ROSANA L.; LASSEGUE, BERNARD; SADIKOT, RUXANA T.; GRIENDLING, KATHY K.; HERNANDES, MARINA S.. Poldip2 mediates blood-brain barrier disruption in a model of sepsis-associated encephalopathy. JOURNAL OF NEUROINFLAMMATION, v. 16, n. 1, NOV 28 2019. (17/14020-4)

PINHEIRO CAMPOS, ANA CAROLINA; KIKUCHI, DANIEL SEICHO; NARDINI PASCHOA, AMANDA FAURE; KUROKI, MAYRA AKEMI; FONOFF, ERICH TALAMONI; HAMANI, CLEMENT; PAGANO, ROSANA LIMA; HERNANDES, MARINA SORRENTINO. Unraveling the Role of Astrocytes in Subthalamic Nucleus Deep Brain Stimulation in a Parkinson's Disease Rat Model. Cellular and Molecular Neurobiology, v. 40, n. 6, p. 939-954, AUG 2020. (17/14020-4, 16/07168-2)