Effects of Specific Multi-Nutrient Enriched Diets on Cerebral Metabolism, Cognition and Neuropathology in AβPPswe-PS1dE9 Mice

Abstract

Recent studies have focused on the use of multi-nutrient dietary interventions in search of alternatives for the treatment and prevention of Alzheimer's disease (AD). In this study we investigated to which extent long-term consumption of two specific multi-nutrient diets can modulate AD-related etiopathogenic mechanisms and behavior in 11-12-month-old AβPPswe-PS1dE9 mice. Starting from 2 months of age, male AβPP-PS1 mice and wild-type littermates were fed either a control diet, the DHA+EPA+UMP (DEU) diet enriched with uridine monophosphate (UMP) and the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), or the Fortasyn® Connect (FC) diet enriched with the DEU diet plus phospholipids, choline, folic acid, vitamins and antioxidants. We performed behavioral testing, proton magnetic resonance spectroscopy, immunohistochemistry, biochemical analyses and quantitative real-time PCR to gain a better understanding of the potential mechanisms by which these multi-nutrient diets exert protective properties against AD. Our results show that both diets were equally effective in changing brain fatty acid and cholesterol profiles. However, the diets differentially affected AD-related pathologies and behavioral measures, suggesting that the effectiveness of specific nutrients may depend on the dietary context in which they are provided. The FC diet was more effective than the DEU diet in counteracting neurodegenerative aspects of AD and enhancing processes involved in neuronal maintenance and repair. Both diets elevated interleukin-1β mRNA levels in AβPP-PS1 and wild-type mice. The FC diet additionally restored neurogenesis in AβPP-PS1 mice, decreased hippocampal levels of unbound choline-containing compounds in wild-type and AβPP-PS1 animals, suggesting diminished membrane turnover, and decreased anxiety-related behavior in the open field behavior. In conclusion, the current data indicate that specific multi-nutrient diets can influence AD-related etiopathogenic processes. Intervention with the FC diet might be of interest for several other neurodegenerative and neurological disorders.

A nutrient combination designed to enhance synapse formation and function improves outcome in experimental spinal cord injury

“…Given orally to rodents, UMP and DHA enhance the levels of biochemical markers for neurites, such as neurofilament-M and neurofilament-70, and the production of dendritic spines (Teather et al, 2002;Sakamoto et al, 2007;Holguin et al, 2008aHolguin et al, , 2008b. In the AßPP-PS1 mouse model of Alzheimer's disease, long-term consumption of FC results in a pronounced shift in the omega-3/omega-6 brain tissue ratio in favour of the omega-3 fatty acids (we found a similar outcome in the red blood cells of rats fed the medium-dose FC-enriched diet for 9 weeks -data not shown), and enhances processes involved in neuronal maintenance and repair (Jansen et al, 2013).…”

Hypertension, cerebrovascular impairment, and cognitive decline in aged AβPP/PS1 mice

“…In accordance, ARA is a mediator of inflammatory pathways, and its metabolites are involved in the production of Aβ and in the pathogenesis of AD 125. In our previous research using the same transgenic mouse model, a multi-nutrient diet was able to induce a pronounced shift in n3/n6 ratio in favor of the n3 fatty acids as compared to the control diet 40. Here, the reduction of the relative n6 content was mainly caused by a decrease in ARA, while the higher n3 content was mainly caused by an increase in DHA.…”

Effect Size Analyses of Souvenaid in Patients with Alzheimer’s Disease

“…These precursors and cofactors are necessary to form neuronal membranes and hypothesized to support the synthesis of new synapses and maintenance of existing synapses [6]. Preclinical studies demonstrated that Fortasyn Connect increases markers of synaptogenesis [3, 7, 8], enhances neurotransmitter synthesis and release [8], preserves white and grey matter integrity [9], improves cerebral blood flow and volume [9], reduces amyloid-β production and toxicity [10, 11], and restores neurogenesis [12], all of which may contribute to an overall neuroprotectiveeffect.…”