| Popis: |
Objectives: Epidemiological evidence demonstrated that patients with obstructive sleep apnea (OSA) are at increased risk for subsequent Parkinson’s disease (PD). However, mechanistic relationship between OSA and PD is unclear. The pathogenesis of OSA-related consequence is assumed to be chronic intermittent hypoxia (CIH). In this study, we plan to test the hypothesis that CIH might facilitate PD progression. Methods: To induce the PD rats, lipopolysaccharide (LPS) was unilaterally injected into the right striatum of the rat brain. The CIH group was treated with intermittent low oxygen for 4 weeks. We used 18F-FE-PE2I positron emission tomography (PET) imaging, a recently developed radioligand for in vivo quantification of dopamine transporter level, and rotarod test to monitor neural and motor degeneration in rats. In addition, time course changes of TREM-1 (triggering receptor expressed on myeloid cell 1) expression in circulating immune cells was examined by flow cytometry. Results: In the PD rats treated with CIH, PET imaging clearly demonstrated a substantial decline in dopaminergic neurons in the LPS-lesioned striatum. The rotarod test showed progressive motor coordination impairment. Additionally, TREM-1 expression in CD11b-positive cells was significantly increased, which also induced a few apoptotic neurons in substantial nigra of the animals. Conclusions: In the PD rat model, CIH will activate TREM-1 positive cells and systemic inflammation, resulting in dopaminergic neuron apoptosis in substantial nigra, worsening dopaminergic neurodegeneration in striatum, and impairing motor coordination. These findings indicate a novel mechanistic pathway that mediates OSA and PD comorbidity. |
