Oxidative stress in the medullary respiratory neurons contributes to respiratory dysfunction in the 6-OHDA model of Parkinson's disease.
Bárbara FalquettoKarina ThiemeMarília B MaltaKarina C E RochaMarina TuppySimone R PotjeCristina AntonialiAlice Cristina RodriguesCarolina D MunhozThiago S MoreiraAna C TakakuraPublished in: The Journal of physiology (2020)
Parkinson's disease (PD) is a neurodegenerative disease caused by dopaminergic neuron death in the substantia nigra (SN). New evidence has revealed that this neurodegeneration is the result of complex interactions between genetic abnormalities, environmental toxins, mitochondrial dysfunction and disruption of the blood-brain barrier (BBB) in the SN. In addition to classic symptoms, PD patients also exhibit respiratory failure. Here, we investigated whether oxidative stress was associated with neurodegeneration in a respiratory group (RG) of 6-OHDA-treated rats, which act as a model of PD. We analysed how oxidative stress affected apoptotic signalling in the RG 30 days after 6-OHDA treatment, shortly before commencement of breathing impairment (40 days). After 30 days, a dihydroethidium assay showed increased oxidative stress in the RG, anti-apoptotic signalling, as shown by an increase in p-Akt and BcL-2 and a decrease in Bax in the caudal aspect of the nucleus of the solitary tract (cNTS), and a decrease in p-p38 and Bax levels in the retrotrapezoid nucleus (RTN); pro-apoptotic signalling was indicated by a decrease in p-Akt and BcL-2 and an increase in Bax in the rostral ventral respiratory group (rVRG) and pre-Botzinger complex (preBotC). miR-34c, a known oxidative stress protector, was downregulated in 6-OHDA animals in the RC. After 40 days of 6-OHDA, the NTS, rVRG, preBotC and RTN exhibited reduced NeuN immunoreactivity, no BBB disruption and an increase in thiobarbituric acid reactivity. We conclude that in the 6-OHDA model of PD, oxidative stress contributes to neurodegeneration in medullary respiratory neurons.
Keyphrases
- oxidative stress
- induced apoptosis
- dna damage
- diabetic rats
- cell death
- ischemia reperfusion injury
- cell proliferation
- signaling pathway
- spinal cord
- respiratory failure
- respiratory tract
- anti inflammatory
- long non coding rna
- endoplasmic reticulum stress
- end stage renal disease
- genome wide
- intensive care unit
- single cell
- depressive symptoms
- mechanical ventilation
- risk assessment
- prognostic factors
- deep brain stimulation
- high speed
- high resolution
- climate change
- smoking cessation
- human health
- sleep quality
- acute respiratory distress syndrome