Deep brain stimulation and Parkinsons Disease: neuroinflammation control as therapeutic target

• Grant number: 18/18695-9
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: January 01, 2019
• End date: November 30, 2021
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Rosana de Lima Pagano
• Grantee: Ana Carolina Pinheiro Campos
• Host Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil

Abstract

Parkinson's Disease (PD) is a complex neurodegenerative disease characterized by progressive loss of dopaminergic neurons, which is associated with a chronic inflammatory response. PD encompasses motor and non-motor symptoms, eminently symptomatic, starting with an effective pharmacological approach that evolves negatively generating extreme complications. At this stage, the gold standard of treatment is the Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN), which has noticeable benefits in the face of the symptoms of the disease. During the candidate's masters program, it was observed that DBS-NST improves motor deficit and pain, without interfering with the depressive behavior of rats submitted to a model of DP. Furthermore, DBS-STN normalizes the staining for astrocytes, microglia and inflammassome in the PD model. Due to the innovative character of the project and its results in the present proposal for a direct PhD, we will continue with the research of the effect of DBS-STN on DP model in rats. In order to do so, we will evaluate the depressive behavior with a new experimental approach and the expression of inflammatory markers MCP-1, IL-4, IL-6, IL-10 and NF-ºB and the BDNF and GDNF growth factors in the Substance Nigra (SN) and striatum. Furthermore, the effect of DBS on disease progression will be investigated with the expression of ±-synuclein in SN. In order to broaden the knowledge about the clinical effectiveness of DBS, the previously described markers will be evaluated and markers of the neurodegenerative process such as GFAP, TGM-2 and DJ-1 in plasma and cerebrospinal fluid of patients with PD, before and 6 months after DBS-STN. We hypothesize that DBS will be able to modulate the inflammatory response in areas compromised in PD. In this work we intend to elucidate the mechanism of action of DBS, focusing on neuroinflammation, aiming the improvement of therapeutic interventions to the patients with PD. (AU)

Scientific publications

(5)

(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)

PINHEIRO CAMPOS, ANA CAROLINA; RUIZ MARTINEZ, RAQUEL CHACON; VATTI AUADA, ALINE VIVIAN; LEBRUN, IVO; FONOFF, ERICH TALAMONI; HAMANI, CLEMENT; PAGANO, ROSANA LIMA. Effect of Subthalamic Stimulation and Electrode Implantation in the Striatal Microenvironment in a Parkinson's Disease Rat Model. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 20, p. 17-pg., 2022-10-01. (16/07168-2, 18/18695-9, 19/13781-7)

BAPTISTA, ABRAHAO FONTES; BALTAR, ADRIANA; OKANO, ALEXANDRE HIDEKI; MOREIRA, ALEXANDRE; CAMPOS, ANA CAROLINA PINHEIRO; FERNANDES, ANA MERCIA; BRUNONI, ANDRE RUSSOWSKY; BADRAN, BASHAR W.; TANAKA, CLARICE; DE ANDRADE, DANIEL CIAMPI; et al. Applications of Non-invasive Neuromodulation for the Management of Disorders Related to COVID-19. FRONTIERS IN NEUROLOGY, v. 11, NOV 25 2020. (19/10760-9, 18/18695-9)

CHAO, LIAW; GONCALVES, ALEXANDRE S. R.; CAMPOS, ANA CAROLINA P.; ASSIS, V, DANIELE; JERONIMO, RODRIGO; KUROKI, MAYRA A.; SANT'ANNA, FERNANDO M.; MEAS, YUNSAN; ROUXEVILLE, YVES; HSING, WU; et al. omparative effect of dense-and-disperse versus non-repetitive and non-sequential frequencies in electroacupuncture-induced analgesia in a rodent model of peripheral neuropathic pai. Acupuncture in Medicine, v. 40, n. 2, NOV 2021. (18/18695-9)

ANTUNES, GEIZA FERNANDA; PINHEIRO CAMPOS, ANA CAROLINA; DE ASSIS, DANIELLE VARIN; GOUVEIA, FLAVIA VENETUCCI; DE JESUS SENO, MIDIA DIAS; PAGANO, ROSANA LIMA; RUIZ MARTINEZ, RAQUEL CHACON. Habenula activation patterns in a preclinical model of neuropathic pain accompanied by depressive-like behaviour. PLoS One, v. 17, n. 7, p. 12-pg., 2022-07-12. (18/18695-9, 11/08575-7, 13/20602-5)

PINHEIRO CAMPOS, ANA CAROLINA; ANTUNES, GEIZA FERNANDA; MATSUMOTO, MARCIO; PAGANO, ROSANA LIMA; RUIZ MARTINEZ, RAQUEL CHACON. Neuroinflammation, Pain and Depression: An Overview of the Main Findings. FRONTIERS IN PSYCHOLOGY, v. 11, JUL 31 2020. (18/18695-9)