Evaluation of autophagy in respiratory nuclei after treatment with apocynin in an animal model of Parkinson's disease

• Grant number: 21/06351-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2021
• End date: September 30, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Bárbara Falquetto
• Grantee: Andre Luiz Ferreira do Nascimento
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 19/00065-1 - Oxidative stress in respiratory control of Parkinson Disease animal model, AP.JP

Abstract

Parkinson's disease (PD) is a neurodegenerative disease with unknown etiology characterized by the loss of catecholaminergic neurons within the Substancia Nigra (SN), what leads to motor and non-motor symptoms. Genetic and environmental factors are responsible for the beginning of the disease, promoting apoptosis through oxidative stress and autophagic signaling. Past studies have also showed impairments in the respiratory pattern in animal models of PD by 6-OHDA, accompanied by oxidative stress, what correlates with impaired autophagy signaling and oxidative stress in post-mortem brains of PD patients. The autophagic flux consists of a cellular homeostatic process that generates the recycling of cellular macromolecules that have lost their function or are no longer useful for the cell. Among the various signaling pathways involved in autophagic flow, the target protein of rapamycin in humans (mTOR) is important in the down-regulation of apoptotic pathways, as well as beclin-1 and LC3, essential in the progression of autophagic flow. Oxidative stress has been repeatedly shown to be essential in the progression of several neurodegenerative diseases, and the production of reactive oxygen species (ROS) by NADPH oxidase also plays an important role in these diseases. The use of NOX inhibitors, the catalytic region of NADPH oxidases, can be both an interesting starting point for studies and for possible therapeutic approaches in the future. In a recent project, the use of the non-specific NOX inhibitor, apocynin, was shown to be able to prevent the neurodegeneration of neurons in the respiratory column in animal models of PD by 6-OHDA. Thus, the objective of this project is to quantitatively evaluate the mRNA of these proteins within the respiratory nuclei through rt-PCR obtained in animal models of PD by 6-OHDA, 30 days after induction, comparing 4 experimental groups: i) Untreated control animals; ii) Treated control animals; iii) 6-OHDA untreated animals and iv) 6-OHDA treated animals, in order to establish relationships regarding autophagic cellular responses against NADPH oxidase inhibition.