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Effect of electroacupuncture on Nrf2/NLRP3/Caspase-1 pathway mediated-pyroptosis in mice with Parkinson's disease
Xiao-Lei Zhang1, Meng-Ni Hu1, Zhen Rong1
1College of Acupuncture-moxibustion and Orthopaedics of Hubei University of Chinese Medicine/Hubei Provincial Collaborative Innovation Center of Preventive Treatment of Diseases by Acupuncture-moxibustion, Wuhan 430060, China.
Objectives:
To observe the effect of electroacupuncture (EA) on nuclear transcription factor E2 related factor 2 (Nrf2)/NOD-like receptor family pyrin domain-containing protein 3 (NLRP3)/cysteine aspartic acid specific protease-1 (Caspase-1) pathway in the substantia nigra (SN) of mice with Parkinson's disease (PD), so as to explore the neuroprotective mechanism of EA.
Methods:
Forty C57BL/6 male mice were randomly divided into 4 groups, namely, control, PD model, EA and sham-EA groups, with 10 mice in each group. The PD mouse model was established by gavage of rotenone for 4 weeks. Mice in the EA group were given EA stimulation (1 mA, 2 Hz) at "Fengfu" (GV36), bilateral "Taichong" (LR3) and "Zusanli" (ST36) for 30 min, once daily for 2 consecutive weeks. And mice in the sham-EA group were given acupuncture at the subcutaneous areas of the same acupoints without EA stimulation. The open-field test was used for assessment of mouse behavior. The levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in the serum were detected by enzyme-linked immunosorbent assay . The positive expression of tyrosine hydroxylase (TH) in SN was determined by immunohistochemistry. The mRNA expression levels of Nrf2, NLRP3, Caspase-1, gasdermin D(GSDMD), IL-1β, IL-18 and the protein expression levels of Nrf2, NLRP3, Caspase-1 and GSDMD in the SN were detected by quantitative real-time PCR and Western blot, separately.
Results:
After modeling, compared with the control group, the behavioral score was increased (P<0.01), the total exercise time, the total distance and the average speed were decreased (P<0.01), and the positive expression of TH and the mRNA and protein expression levels of Nrf2 in the SN were decreased (P<0.01), while the contents of IL-1β and IL-18 in serum, the mRNA and protein expression levels of NLRP3, Caspase-1 and GSDMD and the mRNA expression levels of IL-1β and IL-18 in the SN were up-regulated (P<0.01) in the PD model group. Following EA intervention, the behavioral score was decreased(P<0.01), the total exercise time, total distance and average speed were increased (P<0.01), the positive expression of TH and the mRNA and protein expressions of Nrf2 in SN were up-regulated (P<0.01, P<0.05), while the contents of IL-1β and IL-18 in serum, the mRNA and protein expression levels of NLRP3, Caspase-1 and GSDMD as well as the mRNA expression levels of IL-1β and IL-18 in the SN were down-regulated (P<0.01, P<0.05) in the EA group relative to the PD model and sham-EA groups. There were no significant differences in the above indicators between the PD model and sham-EA groups.
Conclusions:
EA stimulation of GV36, LR3 and ST36 can improve motor deficits, reduce the loss of dopamine neurons in the SN, and inhibit neuroinflammatory responses in mice with PD, which may be related to its effects in regulating the Nrf2/NLRP3/Caspase-1 pathway mediated pyroptosis.
Insights
Electroacupuncture (EA) improves motor function and reduces neuroinflammation in Parkinson's disease (PD) mice by regulating the Nrf2/NLRP3/Caspase-1 pathway. This study explores EA's neuroprotective mechanism against PD.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor deficits and dopaminergic neuron loss.
- Neuroinflammation, involving pathways like Nrf2/NLRP3/Caspase-1, plays a critical role in PD pathogenesis.
- Electroacupuncture (EA) is a potential therapeutic intervention for PD, but its precise neuroprotective mechanisms require elucidation.
Purpose of the Study:
- To investigate the effects of EA on the Nrf2/NLRP3/Caspase-1 pathway in the substantia nigra (SN) of PD mice.
- To explore the neuroprotective mechanisms of EA in a rotenone-induced PD mouse model.
Main Methods:
- A PD mouse model was established using rotenone, with groups including control, PD model, EA, and sham-EA.
- EA stimulation was applied to specific acupoints (GV36, LR3, ST36) for two weeks.
- Behavioral tests, serum cytokine analysis (IL-1β, IL-18), immunohistochemistry (TH), and molecular analyses (qRT-PCR, Western blot) were performed.
Main Results:
- PD model mice exhibited motor deficits, decreased tyrosine hydroxylase (TH) and Nrf2 expression, and increased IL-1β, IL-18, NLRP3, Caspase-1, and GSDMD levels.
- EA treatment significantly improved motor function, increased TH and Nrf2 expression, and reduced inflammatory markers and pyroptosis-related proteins.
- No significant differences were observed between the PD model and sham-EA groups.
Conclusions:
- EA stimulation effectively ameliorates motor deficits and dopaminergic neuron loss in PD mice.
- EA inhibits neuroinflammation by modulating the Nrf2/NLRP3/Caspase-1 pathway and pyroptosis.
- EA demonstrates significant neuroprotective effects against PD, offering a potential therapeutic strategy.
