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

Abstract

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.

Protection effect of piperine and piperlonguminine from Piper longum L. alkaloids against rotenone-induced neuronal injury

“…The current study investigated the mechanism underlying these effects by inducing a PD-like syndrome using rotenone, as evidenced by the diminished performance on the rotarod test and loss of dopaminergic neurons in the midbrain (Fig. 1), which was consistent with results of previous studies that used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to induce PD (Costa et al, 2013;Toy et al, 2013;Lee et al, 2014). An assessment of gait using catwalk analysis revealed that rotenone caused a shortening of print width and length, which is consistent with published reports of 6-OHDAinduced PD (Chuang et al, 2010), (Hsieh et al, 2011) and comparable to what is observed in PD patients who experience rigidity of the muscles that consequently limits movement.…”

Back to the basics: Regular exercise matters in Parkinson's disease: Results from the National Parkinson Foundation QII Registry study

“…There is a substantial body of evidence demonstrating impact of different exercise modalities on PD related disability and some data pointing to potential disease modifying effects of exercise [3]. Physical activity has been hypothesized to reduce the impact of PD through a number of mechanisms.…”

Exercise alters resting-state functional connectivity of motor circuits in parkinsonian rats

“…Long-term treadmill exercise has been shown to partly restore the level of dopamine D 2 receptor binding in the striatum in early PD patients (Fisher, et al, 2013). In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonian mice treadmill running similarly increases D 2 receptor binding (Vuckovic, et al, 2010) and reverses dendritic spine loss (Toy, et al, 2014) in the dorsolateral striatum. Treadmill exercise in rats has also been shown to increase the expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor subunits, synapsin I, synaptophysin, and neurofilaments in the striatum (Garcia, et al, 2012, Real, et al, 2010).…”