Abstract
Parkinson’s disease (PD), caused by destruction of dopaminergic neurons in the brain, leads to motor symptoms like bradykinesia, tremor, and walking impairments. While most research effort focuses on changes in neuronal pathology we examined how muscle proteins were altered in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. A Ca2+ release channel complex, consisting of ryanodine receptors (RYR), triadin (TRDN), and calsequestrin (CSQ1), is important for excitation-contraction coupling in the sarcoplasmic reticulum membrane in muscles. Thus, we investigated changes in the RYR Ca2+ release channel components in PD mice model. Based on a report that TRDN deletion impairs skeletal muscle function, we also investigated how the knock-down of TRDN affects other components of the RYR channel in the PD model. In this study, the expression levels of the components of RYR channels decreased in the quadriceps femoris muscle of MPTP-induced PD mice and in C2C12 cells treated with 1-methyl-4-phenylpyridinium. We show that decreased TRDN levels decrease RYR and CSQ1 levels. These results suggest that the levels of proteins related to Ca2+ channel function decreased in this model, which could impair muscle function. We conclude that muscle function alterations could add to the bradykinesia and tremor in this model of PD.
Highlights
Parkinson’s disease (PD) is a brain disorder that is caused by the degeneration of dopaminergic cells in the substantia nigra (SN)
We developed an MPTP-induced PD mouse model and used it to verify that the expression levels of Ca2+ channel components decreased in the leg quadriceps femoris (QF) muscle
We showed that the expression levels of TRDN, ryanodine receptors (RYR), and CSQ1 were decreased by MPP + treatment in C2C12 cells at the cellular level
Summary
Parkinson’s disease (PD) is a brain disorder that is caused by the degeneration of dopaminergic cells in the substantia nigra (SN). The symptoms of PD include bradykinesia (slow movement), tremor, muscle rigidity, postural instability, and walking impairments. The symptoms related to the neuromuscular function are mainly observed in patients with PD. PD usually occurs in elderly people and causes dangerous situations like falling which can cause secondary injury. Alleviating the symptoms related to muscles will improve the patients’ quality of life. It was shown that bradykinesia could be due to insufficient recruitment of muscle force for the initiation
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