Abstract
Neurotrophins, such as brain-derived neurotrophic factor (BDNF), have shown promise as neuroprotective agents, indicating their potential in therapeutic strategies for neurodegenerative disease. However, the inherent bioactivity and pharmaceutical limitations of BDNF compromise its clinical efficacy. Research has documented the beneficial effects of electroacupuncture (EA) against neurodegeneration, possibly by BDNF-mediated mechanisms. The present study was designed to clarify whether EA can mount a neuroprotective effect in mice lesioned with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) via stimulation of the BDNF-TrkB signaling pathway. We found that EA not only ameliorated the motor dysfunction but also restored the dopaminergic neuronal function and upregulated BDNF expression in MPTP-lesioned mice. Interestingly, the TrkB inhibitor K252a abolished the neuroprotective effects of EA. Western blot analyses further demonstrated that EA might recover the level of phospho-Akt, phospho-ERK1/2, and BDNF against MPTP neurotoxicity via reversing the imbalance between TrkB FL and TrkB T1. Taken together, the results of the present study show that EA stimulation can ameliorate MPTP-induced parkinsonism in mice. Such a neuroprotective effect may be partially mediated via restoring TrkB neurotrophic signaling.
Highlights
Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra par compacta (SNpc) and by impairments in motor function as well as other autonomic nervous system activities (Dexter and Jenner, 2013; Kalia and Lang, 2016)
EA treatment successfully reduced the immobility time for MPTPlesioned mice (79.9±8.877 s (MPTP + EA) vs. 157.8±13.91 s (MPTP + sham EA), n = 10, p = 0.001). Results from both the rotarod test and tail suspension test showed that the 7-day injection of MPTP triggered a severe motor disability in mice, whereas the EA treatment dramatically ameliorated the impairment observed in both the rotarod performance and tail suspension tests
The disruption of the brain-derived neurotrophic factor (BDNF)-TrkB signaling pathway is implicated in neurodegenerative diseases (Andero et al, 2014)
Summary
Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra par compacta (SNpc) and by impairments in motor function as well as other autonomic nervous system activities (Dexter and Jenner, 2013; Kalia and Lang, 2016). The physiological functions of neurotrophins [e.g., nerve growth factor and brain-derived neurotrophic factor (BDNF)] and the related tyrosine kinase receptors (Trks) are affected, subsequently jeopardizing the survival, differentiation, and patterning of neurons (Yamada et al, 2001; Bruno and Cuello, 2012). Ectopic overexpression of BDNF ameliorated the motor dysfunction in 6-OHDA-treated animals (Klein et al, 1999). These studies indicate that BDNF is important for preserving the dopaminergic neurons and preventing or retarding neurodegeneration. Tyrosine kinase receptor type B (TrkB) is well known to mediate the neurotrophic function of BDNF. Neuroprotective therapy is needed to recover the balance of TrkB FL and TrkB T1 (Andero et al, 2014)
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