Endurance exercise training protects against the upregulation of nitric oxide in the striatum of MPTP/probenecid mouse model of Parkinson's disease

NeuroRehabilitation. 2013;32(1):141-7. doi: 10.3233/NRE-130831.


Objectives: Parkinson's disease (PD) is a neurodegenerative disorder, caused by the gradual loss of cells in substantia nigra. Nitric oxide (NO) plays an important role in a variety of signal transduction pathways that are crucial for maintaining the physiologic functions of nervous system. The aims of this study are: 1) To investigate the expression of the inducible form of NO (iNOS), and compare it to neuronal nitric oxide (nNOS) in the brain of a chronic mouse model of PD and 2) To study the effect of endurance exercise training on the expression of these markers.

Method: Mouse models of PD were obtained using 10 doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (25 mg/kg) and probenecid (250 mg/kg) over 5 weeks. Forty C57BL /6 albino mice were randomly divided into four groups: sedentary control (SC, N = 10), exercise control (EC, N = 10), sedentary PD (SPD, N = 10), exercise PD (EPD, N = 10). At the end of training program, nNOS and iNOS were evaluated in the striatum in all animal groups using immunohistochemistry.

Results: nNOS showed significant increases in striatum (ST) of SPD mice compared to SC mice (P > 0.03). There was also decreased expression of nNOS in EC group compared to SC mice, but this decrease was not significant (P > 0.8). Exercise training significantly decreased the level of nNOS in the EPD compared to SPD, (P > 0.04). Although, iNOS expression followed almost the same trend as nNOS, but exercise training did not significantly decrease the expression of iNOS in both EC and EPD groups, P > 0.2 and 0.3 respectively.

Discussion: The data from this study suggests that 4 weeks of treadmill exercise has a positive impact on the expression of nNOS and iNOS in the striatum of a PD model. This might clear in part the pathogenicity of the diseases and the positive impact of training on PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Corpus Striatum / metabolism*
  • Disease Models, Animal
  • Male
  • Mice
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type I / genetics
  • Nitric Oxide Synthase Type I / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / genetics
  • Parkinson Disease, Secondary / metabolism*
  • Physical Conditioning, Animal / physiology*
  • Physical Endurance / physiology*
  • Probenecid
  • Up-Regulation*


  • Nitric Oxide
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Probenecid