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SIRT1/AMPK pathway is involved in neuroprotective effects of resveratrol on MPTP-induced neuron loss

Y.J. Guo, S.Y. Dong, W.J. Zhao, Y.C. Wu (Shanghai, China)

Meeting: 2018 International Congress

Abstract Number: 1332

Keywords: Parkinsonism

Session Information

Date: Monday, October 8, 2018

Session Title: Parkinson's Disease: Genetics

Session Time: 1:15pm-2:45pm

Location: Hall 3FG

Objective: The present study was carried out to observe the neuroprotective effects of RV on MPTP-induced mouse model of PD, and explore its potential neuroprotective mechanism.

Background: Resveratrol (RV), a polyphenolic compound derived from grapes and red wine, can exert a wide range of beneficial effects. Parkinson’s disease (PD) is a progressive neurodegenerative disorder primarily resulting from degeneration of dopaminergic neurons.

Methods: MPTP selectively damages dopaminergic neurons and has been proposed as an experimental animal model to study PD for many decades. Subacute intoxication regimen, which involves one injection of 30 mg/kg/free base MPTP daily for five consecutive days, was applied in our study. RV (100 mg/kg/day) was administrated by intragastric gavage (i.g.). EX527 (10 mg/kg/day), a specific SIRT1 inhibitor, was injected intraperitoneally. Male C57BL/6 mice were divided into four groups (n = 12): CON group, MPTP group, RV+MPTP group, and EX527+RV+MPTP group. Tyrosine hydroxylase (TH) positive cells, protein level of TH, SIRT1, AMPK, p-AMPK, Caspase 3 and Cleaved caspase 3 were determined by immunofluorescence staining and western blot.

Results: MPTP-induced mouse model of PD exhibited loss of dopaminergic neurons, decreased levels of TH (P < 0.001), SIRT1 (P < 0.01), p-AMPK (P < 0.05) and increased level of Cleaved caspase 3 (P < 0.001), in the present study. Administration of RV prevented MPTP-induced dopaminergic neuronal loss, caused up-regulation of SIRT1 (P < 0.001), TH (P < 0.01), p-AMPK (P < 0.01) and down-regulation of Cleaved caspase 3 (P < 0.01). Meanwhile, administration of EX527 reversed the effects of RV stated above, did not prevent MPTP-induced dopaminergic neuronal loss, caused down-regulation of TH (P < 0.001), SIRT1 (P < 0.001), p-AMPK (P < 0.01) and up-regulation of Cleaved caspase 3 (P < 0.01).

Conclusions: SIRT1/AMPK pathway was involved in the neuroprotective effects of RV on MPTP-induced neuron loss.

To cite this abstract in AMA style:

Y.J. Guo, S.Y. Dong, W.J. Zhao, Y.C. Wu. SIRT1/AMPK pathway is involved in neuroprotective effects of resveratrol on MPTP-induced neuron loss [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/sirt1-ampk-pathway-is-involved-in-neuroprotective-effects-of-resveratrol-on-mptp-induced-neuron-loss/. Accessed June 6, 2025.
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