Oxidative Stress Inhibition Via Apocynin Prevents Medullary Respiratory Neurodegeneration and Respiratory Pattern Dysfunction in a 6-Hydroxydopamine Animal Model of Parkinson's Disease

Author(s)

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

• Document type: Journal article
• Source: Neuroscience; v. 502, p. 16-pg., 2022-10-15.

Abstract

Parkinson's Disease (PD) is a neurogenerative disorder characterized by the death of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc), leading to motor, cognitive, learning, and respiratory dysfunctions. New evidence revealed that breathing impairment in PD mainly results from oxidative stress (OS) that initiates apoptotic signaling in respiratory neurons. Here, we investigated the role of OS inhibition using apocynin (non-specific NADPH oxidase inhibitor) in a 6-OHDA PD animal model in the neural control of breathing. The PD model was confirmed with a 70% reduction in TH-expressing neurons within the SNpc. After 20 and 40 days of PD induction, no differences were observed in superoxide anion levels in any respiratory nuclei. At 30 days after PD induction, 6-OHDA animals presented OS that was prevented in all respiratory nuclei by adding apocynin to the drinking water for 10 days. Forty days after PD animal model induction, impaired motor and breathing function, reduced Phox2b and NK1 receptors-expressing neurons in the medullary respiratory areas; decreased latency to fall in the rotarod motor test; and attenuated respiratory frequency and minute ventilation parameters at rest and under hypercapnia conditions were observed. After 20 days of apocynin treatment, neurodegeneration of respiratory nuclei and breathing dysfunction in 6-OHDA animals were prevented. Thus, OS contributes to respiratory neuron death, consequently leading to breathing dysfunction in the 6-OHDA PD animal model. Furthermore, these results present a new perspective for preventing the onset and progression of PD-related respiratory impairments. (C) 2022 IBRO. Published by Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 15/23376-1 - Retrotrapezoid nucleus, respiratory chemosensitivity and breathing automaticity
• Grantee: Thiago dos Santos Moreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/00065-1 - Oxidative stress in respiratory control of Parkinson Disease animal model
• Grantee: Bárbara Falquetto
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 16/03572-3 - The relationship between glucocorticoid receptor activation and the neuronal hyperexcitability in the basolateral amygdala in the restraint stress-induced long-lasting anxiety and their implications in the impaired contextual fear extinction
• Grantee: Carolina Demarchi Munhoz
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/01236-4 - Effects of pharmacological and non-pharmacological treatments on respiratory changes observed in a murine model of Parkinson's disease
• Grantee: Ana Carolina Takakura Moreira
• Support Opportunities: Regular Research Grants