Treadmill exercise reverses dendritic spine loss in direct and indirect striatal medium spiny neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease

Neurobiol Dis. 2014 Mar;63:201-9. doi: 10.1016/j.nbd.2013.11.017. Epub 2013 Dec 5.


Exercise has been shown to be beneficial for Parkinson's disease (PD). A major interest in our lab has been to investigate how exercise modulates basal ganglia function and modifies disease progression. Dopamine (DA) depletion leads to loss of dendritic spines within the caudate nucleus and putamen (striatum) in PD and its animal models and contributes to motor impairments. Striatal medium spiny neurons (MSNs) can be delineated into two populations, the dopamine D1 receptor (DA-D1R)-containing MSNs of the direct pathway and dopamine D2 receptor (DA-D2R)-containing MSNs of the indirect pathway. There is evidence to suggest that the DA-D2R-indirect pathway MSNs may be preferentially affected after DA-depletion with a predominate loss of dendritic spine density when compared to MSNs of the DA-D1R-direct pathway in rodents; however, others have reported that both pathways may be affected in primates. The purpose of this study was to investigate the effects of intensive exercise on dendritic spine density and arborization in MSNs of these two pathways in the MPTP mouse model of PD. We found that MPTP led to a decrease in dendritic spine density in both DA-D1R- and DA-D2R-containing MSNs and 30 days of intensive treadmill exercise led to increased dendritic spine density and arborization in MSNs of both pathways. In addition, exercise increased the expression of synaptic proteins PSD-95 and synaptophysin. Taken together these findings support the potential effect of exercise in modifying synaptic connectivity within the DA-depleted striatum and in modifying disease progression in individuals with PD.

Keywords: Basal ganglia; Dopamine; GFP; Neuroplasticity; Parkinson's; Striatum; Synaptogenesis.

MeSH terms

  • Analysis of Variance
  • Animals
  • Corpus Striatum / pathology*
  • Dendritic Spines / pathology*
  • Dendritic Spines / ultrastructure
  • Disease Models, Animal
  • Exercise Test
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Lysine / analogs & derivatives
  • MPTP Poisoning / pathology*
  • MPTP Poisoning / rehabilitation*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurons / pathology*
  • Neurons / ultrastructure
  • Physical Conditioning, Animal / methods*
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism
  • Silver Staining
  • Time Factors


  • Receptors, Dopamine D2
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • biocytin
  • Lysine