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Deep brain stimulation and Parkinson's disease: Control of the neuroinflammation as a therapeutic target

Grant number: 16/07168-2
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): August 01, 2016
Effective date (End): October 12, 2018
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
Associated scholarship(s):17/14020-4 - Evaluation of high frequency stimulation in the astrocytic response in vitro, BE.EP.MS


Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by progressive loss of dopaminergic neurons, which is mediated by mitochondrial dysfunction, apoptosis, oxidative stress, microglial activation and inflammatory response. DP generates motor and non-motor symptoms and its treatment is eminently symptomatic. The treatments begin 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 brings evident benefits to the motor and non-motor symptoms. In this project, we intend to demonstrate the relationship between prevention of mitochondrial dysfunction, inflammatory response and neuroplasticity control with the therapeutic effect of DBS-STN in an experimental model of PD. To this end, we will evaluate the effect of DBS-STN in rats with nigrostriatal lesion, induced by striatal 6-OHDA, on motor (rotation and immobility), nociceptive (hyperalgesia) and depression (forced swimming test) responses. We will evaluate the dopaminergic deficit by labeling for tyrosine hydroxylase in the substantia nigra (SN) and by apomorphine-induced rotation. Also, we will evaluate the mitochondrial dysfunction, neuronal pattern and glial activation as well as inflammasome and inflammatory response in the SN, striatum, globus pallidus and primary motor cortex, in the presence and absence of DBS-STN. We hypothesized that DBS will be able to modulate the mitochondrial dysfunction and consequently delaying neuronal death by modulating the inflammatory response in compromised areas in PD. With this work we intend to elucidate the mechanism of action of DBS, focusing on neuroinflammation, in order to guide the improvement of the therapeutic interventions for patients with PD.

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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)
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., . (16/07168-2, 18/18695-9, 19/13781-7)
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, . (17/14020-4, 16/07168-2)

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