Promising Effects of Neurorestorative Diets on Motor, Cognitive, and Gastrointestinal Dysfunction after Symptom Development in a Mouse Model of Parkinson's Disease.

Amos Attali,Nick Van Wijk,Johan Garssen,Laus M Broersen,Aletta D Kraneveld,Paula Perez-Pardo,Esther M De Jong

doi:10.3389/fnagi.2017.00057

Abstract

Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic nigrostriatal neurons, with reductions in the function and amount of dopaminergic synapses. Therefore, synapse loss and membrane-related pathology provide relevant targets for interventions in PD. We previously showed the beneficial preventive effects of a dietary intervention containing uridine and DHA, two precursors for membrane synthesis, in the intrastriatal rotenone model for PD. Here, we examined the therapeutic potential of the same dietary intervention on motor, cognitive, and gastrointestinal symptoms. In addition, we tested the effects of an extended nutritional formula based on the same precursors plus other nutrients that increase membrane phospholipid synthesis as well as prebiotic fibers. C57BL/6J mice received a unilateral rotenone injection in the striatum. Dietary interventions started 28 days after surgery, when motor-symptoms had developed. Readout parameters included behavioral tasks measuring motor function and spatial memory as well as intestinal function and histological examination of brain and gut to assess PD-like pathology. Our results show that rotenone-induced motor and non-motor problems were partially alleviated by the therapeutic dietary interventions providing uridine and DHA. The extended nutritional intervention containing both precursors and other nutrients that increase phospholipid synthesis as well as prebiotic fibers was more effective in normalizing rotenone-induced motor and non-motor abnormalities. The latter diet also restored striatal DAT levels, indicating its neurorestorative properties. This is the first study demonstrating beneficial effects of specific dietary interventions, given after full development of symptoms, on a broad spectrum of motor and non-motor symptoms in a mouse model for PD.

Highlights

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease (AD; de Rijk et al, 2000; Nussbaum and Ellis, 2003)
In the present study we examine the therapeutic potential of the same dietary intervention in the intrastriatal rotenone mouse model of PD given after the development of full motor symptoms, i.e., 4 weeks after rotenone injection, to elucidate if the diet has neurorestorative properties
We demonstrated that intrastriatal rotenone injection caused grip strength loss, spatial recognition deficits, and an increase in the amount of reactive enteric glial cells in the colon

Summary

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease (AD; de Rijk et al, 2000; Nussbaum and Ellis, 2003). PD patients develop non-motor symptoms, including cognitive impairment (Aarsland et al, 2003) and gastrointestinal (GI) dysfunctions (Pfeiffer, 2011; Fasano et al, 2015). The most commonly used drug in the treatment of PD is LDopa that compensates for dopaminergic cell loss by enhancing dopamine synthesis in the remaining terminals. This therapy has several side effects (Schrag and Quinn, 2000), it does not prevent dopaminergic neuron degeneration, and has no effects on non-motor symptoms (Lee and Koh, 2015). Considering that some of the non-responsive symptoms like GI dysfunctions may contribute to L-Dopa response fluctuations (Poewe et al, 2010), there is a clear need to develop additional therapies for PD treatment

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