Dietary interventions with strong preventive and therapeutic effects on both motor and non-motor symptoms in a mouse model of parkinson's disease

Introduction. Administration of dietary precursors and cofactors for membrane synthesis may enhance synapse formation relevant for neurodegenerative disorders. Indeed, preventive treatment with the precursors UMP/DHA reduced rotational behavior in the 6-OHDA Parkinson's Disease (PD) model. Here we examined the efficacy of dietary interventions in the rotenone model of PD, inducing both motor and non-motor symptoms, including gastrointestinal dysfunction. In addition, we tested the effects of an extended nutritional formula based on the same precursors. Method. Male C57BL/6J received a unilateral rotenone injection in the striatum (5.4 ug). Dietary interventions started either 1 week before (preventive) or 3 weeks after surgery (therapeutic), when PD-like symptoms had developed. Readout parameters included behavioral tasks as the rotarod, novel object discrimination, grip strength, and inverted screen test, as well as histological examination of brain and gut. Results. Our results show that the preventive UMP/DHA treatment improved rotenone-induced disturbances in rotarod performance and intestinal transit. Similar effects were found in the therapeutic setting, indicating that the diets did not interfere with rotenone toxicity. The therapeutic treatment also alleviated rotenone-induced deficits in novel object discrimination, grip strength, and inverted screen test. Our extended nutritional intervention was more effective than the diet providing UMP/DHA only. Conclusion. This is the first study demonstrating a therapeutic effect of specific dietary interventions in a mouse model of PD. The improved efficacy of the extended nutritional intervention suggests synergies within our specific multi-nutrient approach.