A Specialized Nutritional Formulation Prevents Hippocampal Glial Activation and Memory Impairment Induced by Amyloid-ß Oligomers in Mice.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia in the elderly and is characterized by progressive cognitive decline. Considerable evidence supports an important role of amyloid-ß oligomers (AßOs) in the pathogenesis of AD, including the induction of aberrant glial activation and memory impairment. OBJECTIVE: We have investigated the protective actions of a nutritional formulation, denoted AZ formulation, on glial activation and memory deficits induced by intracerebroventricular (i.c.v.) infusion of AßOs in mice. METHODS: Two-month-old male mice were treated orally with AZ formulation or isocaloric placebo for 30 consecutive days. Microglial and astrocytic activation were analyzed by immunohistochemistry in the hippocampus 10 days after i.c.v. infusion of AßOs (n = 5 mice per experimental condition). Memory loss was assessed by the novel object recognition (NOR) test (n = 6-10 mice per experimental condition). RESULTS: Oral treatment with the AZ formulation prevented hippocampal microglial and astrocytic activation induced by i.c.v. infusion of AßOs. The AZ formulation further protected mice from AßO-induced memory impairment. CONCLUSION: Results suggest that administration of the AZ formulation may comprise a promising preventative and non-pharmacological strategy to reduce brain inflammation and attenuate memory impairment in AD.

Effects of a Nutritional Formulation Containing Caprylic and Capric Acid, Phosphatidylserine, and Docosahexaenoic Acid in Streptozotocin-Lesioned Rats.

BACKGROUND: It has been studied that nutrition can influence Alzheimer's disease (AD) onset and progression. Some studies on rodents using intraventricular streptozotocin (STZ) injection showed that this toxin changes cerebral glucose metabolism and insulin signaling pathways. OBJECTIVE: The aim of the present study was to evaluate whether a nutritional formulation could reduce cognitive impairment in STZ-induced animals. METHODS: The rats were randomly divided into two groups: sham and STZ. The STZ group received a single bilateral STZ-ICV injection (1 mg/kg). The sham group received a bilateral ICV injection of 0.9% saline solution. The animals were treated with AZ1 formulation (Instanth® NEO, Prodiet Medical Nutrition) (1 g/kg, PO) or its vehicle (saline solution) for 30 days, once a day starting one day after the stereotaxic surgery (n = 6-10). The rats were evaluated using the open field test to evaluate locomotor activity at day 27 after surgery. Cognitive performance was evaluated at day 28 using the object recognition test and the spatial version of the Y-maze test. At day 30, the rats were anesthetized with chloral hydrate (400 mg/kg, i.p) and euthanized in order to evaluate IBA1 in the hippocampus. The differences were analyzed using one-way ANOVA with Bonferroni's or Kruskal Wallis with Dunn's post-hoc test. RESULTS/CONCLUSION: STZ-lesioned rats present memory impairment besides the increased microglial activation. The treatment with AZ1 formulation reversed the memory impairment observed in the object recognition test and Y-maze and also reduced IBA1 in CA1 and DG.