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

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.

Improvement of Blood Plasmalogens and Clinical Symptoms in Parkinson’s Disease by Oral Administration of Ether Phospholipids: A Preliminary Report

“…Moreover, it is recently reported that DHA esterified with lysophospholipids is better incorporated into the brain than its nonesterified form [37,38]. It is also reported that the uridine and DHA containing diet prevented rotenone-induced motor and gastrointestinal dysfunctions in rotenoneinduced PD in mice [39]. e capsule used in the present study contains alkyl acyl choline phospholipid (ePC) and CAEP in addition to ethanolamine plasmalogen (ePE) ( Table 1).…”

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

“…These measurements were conducted at least 1 day before animals received levodopa (as described below) to solely analyze the effectiveness of the dietary intervention. From day 65 after surgery onward, i.e., when the AD was shown to have beneficial effects on motor performance in a previous study (Perez-Pardo et al, 2017 ), until day 93 (4 weeks in total), animals from the four different groups underwent motor function and spatial recognition testing once a week after oral administration of saline or one of three doses of levodopa (5, 10 and 20 mg/kg), the order of which was balanced according to a Latin square design (Table 1 ). All animals received a subcutaneous injection of the decarboxylase inhibitor benserazide (6.25 mg/kg) 30 min prior to the oral administration of levodopa.…”

“…Thirty minutes before the oral levodopa administration, all animals received a subcutaneous injection of the decarboxylase inhibitor benserazide (6.25 mg/kg). The rotarod tests and the grip strength test were performed on days 26 and 27 after surgery, i.e., when rotenone-induced motor dysfunctions were fully developed (Perez-Pardo et al, 2017 ) and before the dietary intervention was started. The order of treatments (levodopa and saline) was balanced according to a Latin square design.…”

“…Iso-caloric diets were produced by Research Diet Services (Wijk bij Duurstede, Netherlands) and were based on the CD, i.e., the standard animal food for laboratory rodents AIN-93M (Reeves et al, 1993 ) with 5% fat. For the AD as previously described (Perez-Pardo et al, 2017 ), uridine (0.51 g/100 g diet) was added and part of the lipid blend of CD was replaced by fish oil, providing DHA (0.75 g/100 g diet) and EPA (0.50 g/100 g diet). The AD also contained supplementary amounts of choline, phospholipids, selenium, folic acid and vitamins B6, B12, C, D and E, above standard levels in the CD.…”

“…We recently demonstrated beneficial effects of specific dietary interventions in a mouse model of PD when given therapeutically, i.e., after the full induction of motor symptoms (Perez-Pardo et al, 2017 ). We showed that rotenone-induced motor, cognitive and gastrointestinal dysfunctions were significantly alleviated by the therapeutic dietary intervention containing both precursors and cofactors for phospholipid synthesis as well as prebiotic fibers (Perez-Pardo et al, 2017 ). The purpose of the present study is to see whether levodopa is effective in the rotenone model applied and to examine whether there are interactions and/or additive effects between the diet and levodopa.…”