Neuroprotective effects of endurance exercise against neuroinflammation in MPTP-induced Parkinson's disease mice

Brain Res. 2017 Jan 15;1655:186-193. doi: 10.1016/j.brainres.2016.10.029. Epub 2016 Nov 3.


Parkinson's disease (PD) is one of the main degenerative neurological disorders accompanying death of dopaminergic neurons prevalent in aged population. Endurance exercise (EE) has been suggested to confer neurogenesis and mitigate the degree of seriousness of PD. However, underlying molecular mechanisms responsible for exercise-mediated neuroprotection against PD remain largely unknown. Given the relevant interplay between elevated α-synuclein and neuroinflammation in a poor prognosis and vicious progression of PD and anti-inflammatory effects of EE, we hypothesized that EE would reverse motor dysfunction and cell death caused by PD. To this end, we chose a pharmacological model of PD (e.g., chronic injection of neurotoxin MPTP). Young adult male mice (7 weeks old) were randomly divided into three groups: sedentary control (C, n=10), MPTP (M, n=10), and MPTP + endurance exercise (ME, n=10). Our data showed that EE restored motor function impaired by MPTP in parallel with reduced cell death. Strikingly, EE exhibited a significant reduction in α-synuclein protein along with diminished pro-inflammatory cytokines (i.e., TNF-α and IL-1β). Supporting this, EE prevented activation of Toll like receptor 2 (TLR2) downstream signaling cascades such as MyD88, TRAF6 and TAK-1 incurred by in MPTP administration in the striatum. Moreover, EE reestablished tyrosine hydroxylase at levels similar to C group. Taken together, our data suggest that an EE-mediated neuroprotective mechanism against PD underlies anti-neuroinflammation conferred by reduced levels of α-synuclein. Our data provides an important insight into developing a non-pharmacological countermeasure against neuronal degeneration caused by PD.

Keywords: Endurance exercise; Parkinson's disease; Toll-like receptor-2; Tyrosine hydroxylase; α-synuclein.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Corpus Striatum / immunology*
  • Corpus Striatum / pathology
  • Cytokines / metabolism
  • Exercise Therapy*
  • MPTP Poisoning / immunology*
  • MPTP Poisoning / pathology
  • MPTP Poisoning / therapy*
  • Male
  • Mice, Inbred C57BL
  • Motor Activity / physiology
  • Neuroimmunomodulation / physiology
  • Neuroprotection / physiology*
  • Pars Compacta / immunology*
  • Pars Compacta / pathology
  • Physical Endurance
  • Random Allocation
  • Rotarod Performance Test
  • Running / physiology
  • Sedentary Behavior
  • Toll-Like Receptor 2 / metabolism
  • Tyrosine 3-Monooxygenase / metabolism
  • alpha-Synuclein / metabolism


  • Cytokines
  • Snca protein, mouse
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • alpha-Synuclein
  • Tyrosine 3-Monooxygenase