A specific multi-nutrient enriched diet enhances hippocampal cholinergic transmission in aged rats

Abstract

Fortasyn Connect (FC) is a specific nutrient combination designed to target synaptic dysfunction in Alzheimer's disease by providing neuronal membrane precursors and other supportive nutrients. The aim of the present study was to investigate the effects of FC on hippocampal cholinergic neurotransmission in association with its effects on synaptic membrane formation in aged rats. Eighteen-month-old male Wistar rats were randomized to receive a control diet for 4 weeks or an FC-enriched diet for 4 or 6 weeks. At the end of the dietary treatments, acetylcholine (ACh) release was investigated by in vivo microdialysis in the right hippocampi. On completion of microdialysis studies, the rats were sacrificed, and the left hippocampi were obtained to determine the levels of choline, ACh, membrane phospholipids, synaptic proteins, and choline acetyltransferase. Our results revealed that supplementation with FC diet for 4 or 6 weeks, significantly enhanced basal and stimulated hippocampal ACh release and ACh tissue levels, along with levels of phospholipids. Feeding rats the FC diet for 6 weeks significantly increased the levels of choline acetyltransferase, the presynaptic marker Synapsin-1, and the postsynaptic marker PSD-95, but decreased levels of Nogo-A, a neurite outgrowth inhibitor. These data show that the FC diet enhances hippocampal cholinergic neurotransmission in aged rats and suggest that this effect is mediated by enhanced synaptic membrane formation. These data provide further insight into cellular and molecular mechanisms by which FC may support memory processes in Alzheimer's disease.

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

“…We report here that chronic supplementation with FC modified the biochemical composition of the scar border towards less reactive astrogliosis and decreased levels of inhibitory CSPGs. Levels of Nogo-A are significantly decreased in aged rats when they are fed a FC diet for 6 weeks (Cansev et al, 2015), showing that chronic supplementation with FC can also reduce levels of myelin inhibitor proteins. Therefore, favourable conditions that could support the reinnervation of the injured spinal cord tissue caudal to the lesion site appear to be met after treatment with FC.…”

“…These are provided by FC. A marked increase in membrane phospholipids and in synaptic proteins is seen in the brains of aged rats receiving a supplementation with FC for 6 weeks, and in that of gerbils supplemented with a diet containing choline, UMP, and DHA, the three main precursors of the synthesis of phospholipids, which are found in FC (Wurtman et al, 2006;Cansev and Wurtman, 2007;Cansev et al, 2015). 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.…”

“…They were formulated by Nutricia Research, Nutricia Advanced Medical Nutrition (Utrecht, The Netherlands), manufactured by Research Diets Services (Wijk bij Duurstede, The Netherlands), and presented as hard pellets stored at − 20°C until use, to prevent lipid oxidation, animals receiving fresh pellets daily. Previous studies carried out for up to 6 weeks have shown that all fatty acids were still present in the original amounts at the end of the supplementation period (Cansev et al, 2015).…”

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.…”

Psychophysiological, cognitive and behavioral aspects of malnutrition in Alzheimer’s disease: a review

“…AD also affects organic needs of protein and calories, because the changes in the monophosphate (UMP), choline, phospholipids, folic acid, vitamins B6, B12, C, E and selenium, which are forming precursors neuronal membranes. Preclinical studies have shown increased phospholipid synthesis, dendritic growth and synaptic proteins (CANSEV et al, 2014) and clinical studies have shown that Souvenaid ® preserves the memory and to maintain the functional organization of the brain when evaluated by electroencephalogram in patients with AD (WAAL et al, 2014).…”