Oxidative stress in respiratory control of Parkinson Disease animal model

• Grant number: 19/00065-1
• Support Opportunities: Research Grants - Young Investigators Grants
• Duration: April 01, 2019 - March 31, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Bárbara Falquetto
• Grantee: Bárbara Falquetto
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Ana Carolina Thomaz Takakura ; Carolina Demarchi Munhoz ; Karina Thieme ; Lucia Rossetti Lopes
• Associated grant(s): 19/15064-0 - Multi-User Equipment approved in grant 2019/00065-1: EMKA plethysmography system, AP.EMU
• Associated scholarship(s): 21/08562-4 - Physical exercise prevents respiratory anatomical and functional changes in the Parkinson's Disease model, BP.DD; 21/12538-1 - The role of apoptotic pathway Bax/Bcl-2 and cell survival promoter Wnt/B-catenin in respiratory nuclei of Parkinsons disease under treatment with apocynin, an inhibitor of NOX, BP.MS; 22/02165-6 - Evaluation of glial cells in the respiratory nuclei in an animal model of Parkinson's Disease with apocynin treatment, BP.IC; + associated scholarships 21/06351-6 - Evaluation of autophagy in respiratory nuclei after treatment with apocynin in an animal model of Parkinson's disease, BP.MS; 21/04314-6 - Evaluation of ASK-1 pro-apoptotic dependent signaling of respiratory nuclei in an animal model of Parkinson's Disease treated by apocynin, BP.IC; 20/01831-7 - The role of oxidative stress on the degeneration of medullary respiratory neurons in an animal model of Parkinsons Disease, BP.IC; 19/19810-9 - Respiratory anatomofunctional changes following apocinin treatment in a Parkinson's Disease model, BP.IC - associated scholarships

Abstract

Parkinson's disease (PD) is an idiopathic, chronic and progressive neurodegenerative disease physiopathologically characterized by the loss of dopaminergic neurons from the compact portion of the substantia nigra (SN), resulting from complex interactions between genetic abnormalities, environmental toxins, mitochondrial dysfunction and other cellular processes, as well as rupture of the blood-brain barrier in the SN region. Recent studies have suggested a correlation between cardiorespiratory changes and neurodegeneration in brainstem regions where the major cardiorespiratory nuclei are found (Tuppy et al., 2000, Falquetto et al., 2017). An increase in oxidative stress in the medullary respiratory control regions in the animal model of PD induced by bilateral 6-hydroxydopamine (6-OHDA) injection in the striatum was also observed, which could be a major cause of the observed medullary neurodegeneration. Therefore, this project seeks to evaluate when, in the PD model, oxidative stress becomes evident in the respiratory control nuclei and if it is dependent on the enzyme Nox (NADPH oxidase). In addition, we will evaluate if the treatment with the non-specific inhibitor of this enzyme, apocynin, is capable of reversing oxidative stress and neurodegeneration in the respiratory control regions, leading to an improvement in respiratory function by the reversal of pro-apoptotic signs and autophagy. For this, the functional respiratory evaluations will be performed by whole body plethysmography, neuroanatomical and biochemical experiments. (AU)

Scientific publications

(4)

(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)

AQUINO, YASMIN C.; CABRAL, LAIS M.; MIRANDA, NICOLE C.; NACCARATO, MONIQUE C.; FALQUETTO, BARBARA; MOREIRA, THIAGO S.; TAKAKURA, ANA C.. Respiratory disorders of Parkinson's disease. Journal of Neurophysiology, v. 127, n. 1, p. 1-15, JAN 2022. (15/23376-1, 20/16320-8, 19/00065-1, 19/01236-4)

FALQUETTO, BARBARA; THIEME, KARINA; MALTA, MARILIA B.; ROCHA, KARINA C. E.; TUPPY, MARINA; POTJE, SIMONE R.; ANTONIALI, CRISTINA; RODRIGUES, ALICE C.; MUNHOZ, CAROLINA D.; MOREIRA, THIAGO S.; et al. Oxidative stress in the medullary respiratory neurons contributes to respiratory dysfunction in the 6-OHDA model of Parkinson's disease. JOURNAL OF PHYSIOLOGY-LONDON, v. 598, n. 22, SEP 2020. (19/01236-4, 18/05426-0, 19/00065-1, 18/07087-8, 16/03572-3, 15/23376-1, 15/11268-0)

SABINO-CARVALHO, JEANN L.; FALQUETTO, BARBARA; TAKAKURA, ANA C.; VIANNA, LAURO C.. Baroreflex dysfunction in Parkinson's disease: integration of central and peripheral mechanisms. Journal of Neurophysiology, v. 125, n. 4, p. 1425-1439, APR 2021. (19/00065-1, 19/01236-4)

NASCIMENTO, ANDRE L. F.; MEDEIROS, PAMELA O. S.; PEDRAO, LUIZ F. A. T.; QUEIROZ, VITORIA C.; OLIVEIRA, LUIZ M.; NOVAES, LEONARDO S.; CAETANO, ARIADINY L.; MUNHOZ, CAROLINA D.; TAKAKURA, ANA C.; FALQUETTO, BARBARA. Oxidative Stress Inhibition Via Apocynin Prevents Medullary Respiratory Neurodegeneration and Respiratory Pattern Dysfunction in a 6-Hydroxydopamine Animal Model of Parkinson's Disease. Neuroscience, v. 502, p. 16-pg., 2022-10-15. (15/23376-1, 19/00065-1, 16/03572-3, 19/01236-4)