Abstract
Parkinson's disease (PD) is a common neurodegenerative disease with movement and balance impairments. Although studies have reported improvement of motor symptoms with physical exercise, the mechanisms by which exercise is beneficial remains poorly understood. Our study addresses the exercise-induced changes to peripheral immune cells by interrogating the transcriptome of blood-derived leukocytes in PD patients before and after exercise. Patients attended 1 h exercise classes twice a week for 12 weeks. Leukocytes were collected at the beginning and end of the study for gene expression analysis by RNA-seq or quantitative real-time PCR. We correlated differentially expressed genes after exercise with clinical measures and analyzed the potential functions of gene changes with Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology analysis. Exercise improved measures of movement and balance when compared with scores before the exercise program. Among the gene changes, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis suggests that T-cell receptor signaling, T-cell activation, and T-cell migration pathways were downregulated, while the T-cell receptor signaling pathway was the most significantly correlated with clinical measures. To further investigate T-cell-related changes in PD leukocytes, we reanalyzed the differentially expressed genes from publicly available microarray data and found that genes in the T-cell activation, differentiation, and migration pathways were upregulated in PD samples compared to controls in a time-dependent manner. Together, our findings suggest that exercise rehabilitation may improve movement and balance in PD patients by reversing the upregulated T-cell activation pathways associated with PD. This study was registered with the Chinese Clinical Trial Registry under ChiCTR-TRC-14004707. Registered on May 27, 2014.
Highlights
Parkinson’s disease (PD) is a common neurodegenerative disease characterized by loss of dopaminergic neurons in substantia nigra and accumulation of aggregated alpha-synuclein in the brain stem, spinal cord, and cortical regions [1]
Two studies have already been completed with more than 100 PD patients in each study [22, 42]. Both studies focused on the molecular markers of PD, and they reported that functions related to metabolism, oxidation, and ubiquitination/proteasomal activity are dysregulated in PD patients
DEG analysis showed the TNFRSF18, a T-cell activation related gene was among the most downregulated genes after exercise and had the strongest correlation with clinical measures. Among those regulated pathways and biological processes, we found that the T-cell receptor signaling pathway was most involved before and after exercise, and it had a significant correlation with our clinical measures
Summary
Parkinson’s disease (PD) is a common neurodegenerative disease characterized by loss of dopaminergic neurons in substantia nigra and accumulation of aggregated alpha-synuclein in the brain stem, spinal cord, and cortical regions [1]. Especially postural instability, adversely affect the daily function and quality of life of patients with PD [2]. Motor symptoms are alleviated with drug therapy, balance impairments are not optimally controlled by pharmacotherapy and require alternative approaches. Exercise has been shown to slow the deterioration of motor symptoms and prolong functional independence [2,3,4], improve movement [3, 4] and balance [5], and decrease the incidence of falls [5,6,7,8,9]. The mechanisms by which exercise is beneficial in patients with PD have not been fully elucidated
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