Oxidative Stress Inhibition via Apocynin Prevents Contributes to Medullary Respiratory Neurodegeneration and Respiratory Pattern Dysfunction in 6-hydroxydopamine Animal Model of Parkinson's Disease.

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 result from oxidative stress (OS) that starts apoptotic signaling in respiratory neurons. Here, we investigated the role of OS inhibition using apocynin (NADPH oxidase non-specific inhibitor) in a 6-OHDA animal model of PD in the neural control of breathing. PD model was confirmed with 70% of reduction in TH-expressing neurons within the SNpc. After 20 and 40 days of PD induction, no differences were observed in the superoxide anion expression in all respiratory nuclei. At 30 days after PD induction 6-OHDA animals presented OS that was prevented by apocynin treatment at drinking water for 10 days in all respiratory nuclei. Forty days after PD animal model induction, we confirmed the motor and breathing impairment; Phox2b and NK1 receptors-expressing neurons reduction in the medullary respiratory areas; decrease in the latency to fall in rotarod motor test; and reduction in respiratory frequency and minute ventilation parameters at rest and hypercapnia conditions. 6-OHDA animals treated for 20 days with apocynin at drinking water prevented the neurodegeneration of respiratory nuclei and the breathing dysfunction. Taken together, these findings show an important role of oxidative stress in the consequent death of respiratory neurons and breathing dysfunction in 6-OHDA PD animal model, paving a new perspective to further translational medicine treatment to prevent PD respiratory impairments.