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

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

•6-OHDA Parkinson’s disease (PD) animal model causes significant respiratory deficits.•Apocynin prevents oxidative stress (OS) in respiratory nuclei in the 6-OHDA model.•Apocynin-mediated OS inhibition reduces respiratory neurodegeneration in the 6-OHDA model.•Apocynin inhibits OS, which prevents br...

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Bibliographic Details
Published in:Neuroscience Vol. 502; pp. 91 - 106
Main Authors: Nascimento, André L.F., Medeiros, Pamela O.S., Pedrão, Luiz F.A.T., Queiroz, Vitoria C., Oliveira, Luiz M., Novaes, Leonardo S., Caetano, Ariadiny L., Munhoz, Carolina D., Takakura, Ana C., Falquetto, Barbara
Format: Journal Article
Language:English
Published: Elsevier Ltd 15-10-2022
Subjects:
6-OHDA
breathing control
medulla
NADPH oxidase
oxidative stress
medulla
APO
DHE
6-OHDA
CNS
PFA
NOD2
RTN
Te
Ti
NADPH oxidase
HCVR
breathing control
EOH
DTPA
cNTS
KO
OS
SNpc
CPu
fR
rVRG
preBotC
VE
PB
iNTS
PD
TH
LC
PAG
ROS
MPTP
oxidative stress
VT
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Summary:•6-OHDA Parkinson’s disease (PD) animal model causes significant respiratory deficits.•Apocynin prevents oxidative stress (OS) in respiratory nuclei in the 6-OHDA model.•Apocynin-mediated OS inhibition reduces respiratory neurodegeneration in the 6-OHDA model.•Apocynin inhibits OS, which prevents breathing impairment in the 6-OHDA PD model.•A new perspective to improve breathing and the quality of life of PD patients is provided. 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.
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ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2022.07.034