Additive Effects of Levodopa and a Neurorestorative Diet in a Mouse Model of Parkinson’s Disease

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...

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Main Authors: Paula Perez-Pardo, Laus M. Broersen, Tessa Kliest, Nick van Wijk, Amos Attali, Johan Garssen, Aletta D. Kraneveld
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-08-01
Series:Frontiers in Aging Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fnagi.2018.00237/full
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spelling doaj-5722a693e47e447d956fbd802f0b598b2020-11-24T22:44:34ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652018-08-011010.3389/fnagi.2018.00237383987Additive Effects of Levodopa and a Neurorestorative Diet in a Mouse Model of Parkinson’s DiseasePaula Perez-Pardo0Laus M. Broersen1Laus M. Broersen2Tessa Kliest3Nick van Wijk4Amos Attali5Johan Garssen6Johan Garssen7Aletta D. Kraneveld8Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, NetherlandsDivision of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, NetherlandsNutricia Research, Utrecht, NetherlandsDivision of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, NetherlandsNutricia Research, Utrecht, NetherlandsNutricia Research, Utrecht, NetherlandsDivision of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, NetherlandsNutricia Research, Utrecht, NetherlandsDivision of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, NetherlandsThough 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.https://www.frontiersin.org/article/10.3389/fnagi.2018.00237/fullParkinson’s diseaselevodopadietary interventionmotor-symptomsnon-motor symptoms
collection DOAJ
language English
format Article
sources DOAJ
author Paula Perez-Pardo
Laus M. Broersen
Laus M. Broersen
Tessa Kliest
Nick van Wijk
Amos Attali
Johan Garssen
Johan Garssen
Aletta D. Kraneveld
spellingShingle Paula Perez-Pardo
Laus M. Broersen
Laus M. Broersen
Tessa Kliest
Nick van Wijk
Amos Attali
Johan Garssen
Johan Garssen
Aletta D. Kraneveld
Additive Effects of Levodopa and a Neurorestorative Diet in a Mouse Model of Parkinson’s Disease
Frontiers in Aging Neuroscience
Parkinson’s disease
levodopa
dietary intervention
motor-symptoms
non-motor symptoms
author_facet Paula Perez-Pardo
Laus M. Broersen
Laus M. Broersen
Tessa Kliest
Nick van Wijk
Amos Attali
Johan Garssen
Johan Garssen
Aletta D. Kraneveld
author_sort Paula Perez-Pardo
title Additive Effects of Levodopa and a Neurorestorative Diet in a Mouse Model of Parkinson’s Disease
title_short Additive Effects of Levodopa and a Neurorestorative Diet in a Mouse Model of Parkinson’s Disease
title_full Additive Effects of Levodopa and a Neurorestorative Diet in a Mouse Model of Parkinson’s Disease
title_fullStr Additive Effects of Levodopa and a Neurorestorative Diet in a Mouse Model of Parkinson’s Disease
title_full_unstemmed Additive Effects of Levodopa and a Neurorestorative Diet in a Mouse Model of Parkinson’s Disease
title_sort additive effects of levodopa and a neurorestorative diet in a mouse model of parkinson’s disease
publisher Frontiers Media S.A.
series Frontiers in Aging Neuroscience
issn 1663-4365
publishDate 2018-08-01
description 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.
topic Parkinson’s disease
levodopa
dietary intervention
motor-symptoms
non-motor symptoms
url https://www.frontiersin.org/article/10.3389/fnagi.2018.00237/full
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