Abstract
Though Parkinson’s disease (PD) clinical picture is generally dominated by motor impairment, non-motor symptoms, such as cognitive decline and gastrointestinal dysfunctions, may develop before motor symptoms and have major effects on quality of life. L-3,4-di-hydroxy-phenylalanine (Levodopa) is the most commonly used treatment of motor symptoms but has serious side-effects with prolonged use and does not stop the degenerative process. Moreover, gastrointestinal dysfunctions interfere with the absorption of levodopa and modify its effectiveness. Since most patients are on levodopa treatment, there is a need for combinational therapies that allow for an effective reduction of both motor and non-motor symptoms. We have recently shown that a diet containing precursors and cofactors required for membrane phospholipid synthesis, as well as prebiotic fibers, had therapeutic effects in a PD mouse model. We now investigate the effects of combined administration of the same diet together with levodopa in the rotenone model of PD. Mice were injected with rotenone or vehicle in the striatum. The dietary intervention started after full induction of motor symptoms. The effects of dietary intervention and oral treatment with different doses of levodopa were assessed weekly. Motor and cognitive functions were tested, intestinal transit was analyzed and histological examination of the brain and the colon was assessed. Our results confirm our previous findings that rotenone-induced motor and non-motor problems were alleviated by the Active diet (AD). Levodopa showed an additive beneficial effect on rotarod performance in rotenone-treated animals fed with the AD. No negative interaction effects were found between the AD and levodopa. Our findings suggest that the dietary intervention might confer additional clinical benefits on patients receiving levodopa treatment.
Highlights
Parkinson’s disease (PD) is the second most frequent age-related neurodegenerative disorder for which there is no cure
There was an overall effect of levodopa on the animals’ motor performances (F(1,92) = 24.77, p < 0.0001 for the rotarod test and F(1,92) = 4.6, p < 0.05 for the grip strength test) and an interaction effect between surgery and levodopa treatment in both the rotarod test (F(1,92) = 27.66, p < 0.0001) and the grip strength test (F(1,92) = 4.12, p < 0.05). These main and interaction effects indicate an increase in motor function for rotenone-injected mice treated with levodopa (20 mg/kg) as compared to rotenoneinjected mice treated with saline, while levodopa administration had no effect on motor performance in sham-treated mice (Figure 1). (F(1,44) = 48.63, p < 0.0001)
We demonstrate that the oral administration of levodopa positively affects motor symptoms in the intrastriatal rotenone model of PD since the rotenone-injected animals orally treated with levodopa showed a better performance on the rotarod test and an improved forelimb grip strength
Summary
Parkinson’s disease (PD) is the second most frequent age-related neurodegenerative disorder for which there is no cure. PD is considered as a movement disorder, but many patients suffer from non-motor symptoms (Lee and Koh, 2015), including olfactory and sleep disturbances (Ross et al, 2006; Haehner et al, 2009; Ponsen et al, 2009), depression (Reijnders et al, 2008), cognitive decline with regard to visuospatial perception and working memory (Aarsland et al, 2003), and gastrointestinal dysfunctions (Savica et al, 2009; Jost, 2010; Pfeiffer, 2011; Fasano et al, 2015) These symptoms may precede the motor phase by decades (Abbott et al, 2001; Gao et al, 2011; Chen et al, 2015), have a major effect on the quality of life (Schrag et al, 2000; Martinez-Martin et al, 2011; Müller et al, 2013) and remain undertreated (Chaudhuri and Schapira, 2009). PD-associated gastrointestinal dysfunction might exacerbate levodopa response fluctuations (Poewe et al, 2010) and on-off oscillations (Hardoff et al, 2001; Müller et al, 2006; Doi et al, 2012; Marrinan et al, 2014)
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