Parkinson's disease (PD) is a neurodegenerative disease with a progressive loss of mesencephalic dopaminergic neurons of the substantia nigra (SN). To further evaluate its pathophysiology, accurate animal models are needed. The current study aims to verify the impact of a 6-hydroxydopamine (6-OHDA) bilateral microinjection into the SN on gastrointestinal symptoms in rats and confirm that the 6-OHDA rat model is an appropriate tool to investigate the mechanisms of Parkinsonian GI disorders. Immunohistochemistry, digital X-ray imaging, short-circuit current, FITC-dextran permeability and ultra-performance liquid chromatography tandem mass spectrometry were used in this study. The results indicated that the dopaminergic neurons in SN and fibres in the striatum were markedly reduced in 6-OHDA rats. The 6-OHDA rats manifested reductions in occupancy in a rotarod test and increases in daily food debris but no difference in body mass or daily consumption. Compared with control rats, faecal pellets and their contents were significantly decreased, whereas gastric emptying and intestinal transport were delayed in 6-OHDA rats. The increased in vivo FITC-dextran permeability and decreased intestinal transepithelial resistance in the model suggest attenuated barrier function in the digestive tract in the PD model. Moreover, inflammatory factors in the plasma showed that pro-inflammatory factors IL-1? and IL-8 were significantly increased in 6-OHDA rats. Collectively, these findings indicate that the model is an interesting experimental tool to investigate the mechanisms involved in the progression of gastrointestinal dysfunction in PD.
- MeSH
- gastrointestinální nemoci chemicky indukované diagnostické zobrazování patofyziologie MeSH
- krysa rodu Rattus MeSH
- oxidopamin toxicita MeSH
- parkinsonské poruchy chemicky indukované diagnostické zobrazování patofyziologie MeSH
- potkani Sprague-Dawley MeSH
- sympatolytika toxicita MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- oxidopamin MeSH
- sympatolytika MeSH
Breathing impairments, such as an alteration in breathing pattern, dyspnoea, and sleep apnoea, are common health deficits recognised in Parkinson's disease (PD). The mechanism that underlies these disturbances, however, remains unclear. We investigated the effect of the unilateral damage to the rat nigrostriatal pathway on the central ventilatory response to hypercapnia, evoked by administering 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle (MFB). The respiratory experiments were carried out in conscious animals in the plethysmography chamber. The ventilatory parameters were studied in normocapnic and hyperoxic hypercapnia before and 14 days after the neurotoxin injection. Lesion with the 6-OHDA produced an increased tidal volume during normoxia. The magnified response of tidal volume and a decrease of breathing frequency to hypercapnia were observed in comparison to the pre-lesion and sham controls. Changes in both respiratory parameters resulted in an increase of minute ventilation of the response to CO(2) by 28% in comparison to the pre-lesion state at 60 s. Our results demonstrate that rats with implemented unilateral PD model presented an altered respiratory pattern most often during a ventilatory response to hypercapnia. Preserved noradrenaline and specific changes in dopamine and serotonin characteristic for this model could be responsible for the pattern of breathing observed during hypercapnia.
- MeSH
- fasciculus telencephali medialis účinky léků fyziologie MeSH
- hyperkapnie patofyziologie MeSH
- krysa rodu Rattus MeSH
- oxidopamin toxicita MeSH
- parkinsonské poruchy chemicky indukované patofyziologie MeSH
- plicní ventilace účinky léků fyziologie MeSH
- potkani Wistar MeSH
- sympatolytika toxicita MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- oxidopamin MeSH
- sympatolytika MeSH
