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

Abstract

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.

Paeonol Ameliorates Cognitive Deficits in Streptozotocin Murine Model of Sporadic Alzheimer’s Disease via Attenuation of Oxidative Stress, Inflammation, and Mitochondrial Dysfunction

“…Additionally, paeonol treatment of ICV STZ groups was dose-dependently associated with lower hippocampal level of oxidative stress and neuroinflammation, attenuation of hippocampal AChE activity, mitochondrial dysfunction, and neutrophil infiltration, and mitigation of astrogliosis. Bilateral ICV injection of STZ produces a well-accepted and consistent model to mimic sAD (Verma et al 2020) with development of cognitive impairments in Y maze (Moura et al 2020), novel object recognition test (Moura et al 2020), Barnes maze (Zappa Villar et al 2018), and passive avoidance (Baluchnejadmojarad and Roghani 2006). Similarly, we observed such impairments in our ICV STZ group as shown by lower alternation in Y maze and decreased discrimination index in novel object recognition paradigm, higher number of errors and greater latency in the probe trial of Barnes maze, and reduction of step-through latency in passive avoidance test.…”

Andrographolide Attenuates Short-Term Spatial and Recognition Memory Impairment and Neuroinflammation Induced by a Streptozotocin Rat Model of Alzheimer’s Disease

“…Yet, the lesion factor was the only factor showing signi cant differences, indicating that the STZ infusion was the responsible for the decrease in locomotion frequency not the ANDRO treatment. It is known that changes in these parameters could decrease the animals' performance in subsequent cognitive tests (Moura et al 2020). However, the exploratory behavior and/or ambulation seem to have been affected only in the OFT, the groups did not show differences in the total time spent exploring the objects in the OLT and in the ORT, in addition, there were no differences in the distance covered in the Y maze and in the number of entries in the arms.…”

“…Stereotaxic surgery was carried out as previously described (Bassani et al, 2017b;Bassani et al, 2017a;Moura et al, 2020). The animals were anesthetized with sodium thiopental (30 mg/kg, i.p.)…”

“…The effects of ANDRO on the microglia in the HIP and PFC of ICV-STZ rats were explored, and immunostaining to identify microglia was carried out using Iba-1 primary antibody. Brain sample processing and immunohistochemistry reactions were developed as described by Moura et al (2020).…”

“…Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder and is mainly characterized by progressive and slow memory loss, especially memory related to recent events and spatial disorientation (Salardini 2019; Moura et al 2020). Late-onset AD, or sporadic AD (sAD), is the preponderant form of the disease, despite its unclear etiology many molecular disturbances have been detected in the sAD aging brain (Correia et al 2011).…”