Electro-Acupuncture Ameliorated MPTP-Induced Parkinsonism in Mice via TrkB Neurotrophic Signaling

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.

Electro-acupuncture alleviates motor deficits and maladaptive striatal plasticity in partial-lesioned parkinsonian mice

“…Evidences revealed that acupuncture or EA could ameliorate motor symptoms and reduce dopaminergic neuronal degeneration in PD models [35][36][37][38]. In our present experiment, chronic EA treatment ameliorated gross motor signs (ambulatory activity and coordinated balance ability) and ne forelimb motor performance in a partial-lesioned model.…”

“…2a, c). Contrasting with application of EA immediately after toxic administration [35] [36] [37], we delivered EA two weeks after 6-OHDA lesion. Thus, it is speculated that chronic 6-OHDA lesion induced irreversible neuronal death in the SNc which could not be reversed by subsequent EA treatment [39].…”

“…Thus, it is speculated that chronic 6-OHDA lesion induced irreversible neuronal death in the SNc which could not be reversed by subsequent EA treatment [39]. Although the different acupoints were utilized in other studies [35,37], EA performed at these acupoints (ST36 and SP6) is known to effectively relieve motor symptoms in PD mice [24,26]. Thus, EA achieves its motor effect in the early stage of the disease by modulating the striatal function without restoring the loss of nigral dopaminergic neurons.…”

Botanical Drug Puerarin Promotes Neuronal Survival and Neurite Outgrowth against MPTP/MPP+-Induced Toxicity via Progesterone Receptor Signaling

“…Mice were evaluated for motor impairments with a rotarod apparatus (Harvard apparatus, Holliston, MA, USA) as described [ 26 , 27 ]. In brief, at 3 days after last dosage of MPTP treatment, mice were subjected to behavioral assessments.…”

Regulation of BDNF-TrkB Signaling and Potential Therapeutic Strategies for Parkinson’s Disease

“…Moreover, TrkB cleavage by calpain impairs the BDNF function [73]. Furthermore, MPTP increased the level of TrkB.T1 expression [74]. Additionally, Rbfox1 (RNA-binding protein fox-1 homolog), a neuron-specific splicing factor, was one among the most consistently upregulated genes identified in the transcriptome of midbrain dopaminergic (mDA) neurons of PD patients [75].…”