title: 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.
authors.affiliation: Department of Pharmacology, Uludag University Medical School, Bursa, Turkey. Electronic address: mcansev@uludag.edu.tr.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Cansev
authors.affiliation: Nutricia Research, Nutricia Advanced Medical Nutrition, Utrecht, the Netherlands.
authors.forename: Nick
authors.initials: N
authors.lastname: van Wijk
authors.affiliation: Department of Pharmacology, Uludag University Medical School, Bursa, Turkey.
authors.forename: Mesut
authors.initials: M
authors.lastname: Turkyilmaz
authors.affiliation: Department of Pharmacology, Uludag University Medical School, Bursa, Turkey.
authors.forename: Fulya
authors.initials: F
authors.lastname: Orhan
authors.affiliation: Nutricia Research, Nutricia Advanced Medical Nutrition, Utrecht, the Netherlands.
authors.forename: John W C
authors.initials: JW
authors.lastname: Sijben
authors.affiliation: Nutricia Research, Nutricia Advanced Medical Nutrition, Utrecht, the Netherlands.
authors.forename: Laus M
authors.initials: LM
authors.lastname: Broersen
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease / Q000503:physiopathology / Q000628:therapy; D000824:Animal Nutritional Physiological Phenomena / Q000502:physiology*; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D059329:Cholinergic Neurons / Q000502:physiology*; D004032:Diet; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D008297:Male; D017208:Rats, Wistar; D013570:Synaptic Membranes / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D002795:Choline O-Acetyltransferase; D000109:Acetylcholine
keywords: Acetylcholine release; Aged rat; Alzheimer's disease; Choline acetyltransferase; Cholinergic neurotransmission; Fortasyn connect; Phospholipid; Souvenaid; Synaptic membrane