Treadmill exercise alleviates neuronal damage by suppressing NLRP3 inflammasome and microglial activation in the MPTP mouse model of Parkinson's disease

Brain Res Bull. 2021 Sep:174:349-358. doi: 10.1016/j.brainresbull.2021.06.024. Epub 2021 Jul 2.

Abstract

Treadmill exercise has been recognized as an effectively therapeutic strategy for Parkinson's disease (PD). However, its exact molecular mechanism of promoting PD remain unclear. Recently, the NLRP3 inflammasome is considered to play a critical role in the pathogenesis of PD. In this study, we investigated whether NLRP3 inflammasome was involved in treadmill exercise-induced neuroprotection and anti-inflammation effect in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. 8-week-old male mice (C57BL/6 strain) were divided into four groups: Control, MPTP, MPTP + EX and EX. MPTP was intraperitoneally injected into mice to establish chronic PD model. The open-field test and pole test were used to assess motor function. The results showed that treadmill exercise significantly alleviated motor dysfunction and dopaminergic neuron degeneration induced by MPTP. In addition, we also found that treadmill exercise suppressed MPTP-triggered microglia activation and the co-localization of NLRP3+/Iba-1+ cells in the substantia nigra. These effects were associated with suppression NLRP3 inflammasome via down-regulation of TLR4/MyD88/NF-κB pathway. Overall, our study demonstrated that treadmill exercise could effectively alleviates neuronal damage via inhibition of NLRP3 inflammasome and microglial activation in MPTP-induced PD mouse model.

Keywords: Inflammasome; Neuroinflammation; Parkinson’s disease; TLR4; Treadmill exercise.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Exercise Therapy
  • Inflammasomes / genetics*
  • MPTP Poisoning / pathology*
  • MPTP Poisoning / therapy*
  • Macrophage Activation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / immunology*
  • Myeloid Differentiation Factor 88 / drug effects
  • NF-kappa B / drug effects
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics*
  • Neurons / pathology*
  • Parkinson Disease, Secondary / pathology*
  • Parkinson Disease, Secondary / therapy*
  • Physical Conditioning, Animal / physiology*
  • Signal Transduction / drug effects
  • Substantia Nigra / pathology
  • Toll-Like Receptor 4 / drug effects

Substances

  • Inflammasomes
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4