Sex differences in the performance of cognitive tasks in a murine model of metabolic syndrome.

The metabolic syndrome includes changes in blood glucose levels, arterial hypertension, triglycerides, dyslipidemia and central obesity. Countless reports have described the correlation between the metabolic syndrome and cognitive impairment. However, only a few reports have assessed cognitive impairment associated with the metabolic syndrome in animals of both sexes. For this purpose, Sprague-Dawley male and female rats were fed either with a hypercaloric diet as model of the metabolic syndrome or with a standard chow diet as controls. Subsequently, spatial learning and memory (Morris water maze) as well as short- and long-term memory (passive avoidance task) were evaluated. Body weight, blood pressure, triglycerides, and total cholesterol significantly increased (F(1, 36) = 94.89, p < .001) in rats fed with hypercaloric diet compared to control rats. Furthermore, cognitive impairment was observed in spatial learning and spatial memory on male rats but not on female rats fed with hypercaloric diet. In addition, a long-term memory impairment was observed in both groups fed with hypercaloric diet in comparison to their respective control group (F(1, 32) = 10.61, p = .0027). Immunohistochemistry results showed no changes in the number of positive cells for NeuN, GFAP and Ox-42. In males fed with a hypercaloric diet, a decrease in testosterone levels was observed, whereas estradiol levels decreased in females when compared with their respective control group (p < .0001). In this MetS animal model, metabolic and cognitive differences were observed in males and females, which demonstrates that sex hormones play a significant role in metabolic regulation and neuroprotection related to the CA1 region of the hippocampus.

The Cracked Potential of Boron-containing Compounds in Alzheimer's Disease.

Alzheimer's disease (AD) is a relevant neurodegenerative disease worldwide. Its relevancy is mainly due to its high prevalence and high global burden. Metalloids have attracted attention as their serum levels seem to differ between affected patients and healthy individuals. On the other hand, atoms of some metalloids have been included in bioactive molecules, exerting some interesting effects, mainly due to their ameliorative effects in neurodegeneration. In this sense, boron-containing compounds (BCC) have been explored to regulate or prevent neurodegeneration. As an example, boric acid has been reported as a compound with antioxidant, anti-inflammatory and neurotrophic effects. Other natural BCCs have also shown amelioration of metabolic conditions often related to increased risk of neurodegenerative maladies. However, in recent years, additional organoboron compounds have been reported as active in several processes linked to neurodegeneration and especially attractive as regulators of the origin and progression of AD. In this mini-review, some data are collected suggesting that some natural BCC could be used as preventive agents, but also the potential of some BODIPYs as tools for diagnosis and some other BCC (particularly boronic acids and pinacol boronic esters) for acting as promising therapeutic agents for AD.

Neuroprotective Effects of Apocynin and Galantamine During the Chronic Administration of Scopolamine in an Alzheimer's Disease Model.

Alzheimer's disease (AD) is one of the most complicated neurodegenerative diseases, and several hypotheses have been associated with its development and progression, such as those involving glucose hypometabolism, the cholinergic system, calcium imbalance, inflammation, oxidative imbalance, microtubule instability, and the amyloid cascade, several of which are related to oxidative stress (free radical generation), which contributes to neuronal death. Therefore, several efforts have been made to establish a sporadic AD model that takes into account these hypotheses. One model that replicates the increase in amyloid beta (Aß) and oxidative stress in vivo is the scopolamine model. In the present work, the chronic administration (6 weeks) of scopolamine was used to analyze the neuroprotective effects of apocynin and galantamine. The results showed that scopolamine induced cognitive impairment, which was evaluated 24 h after the final dose was administered. In addition, after scopolamine administration, the Aß and superoxide anion levels were increased, and NADPH oxidase 2 (NOX2), nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor kappa B (NFkB) genes were overexpressed. These effects were not observed when either apocynin or galantamine was administered during the last 3 weeks of scopolamine treatment, and although the results from both molecules were related to lower Aß production and, consequently, lower superoxide anion production, they were likely realized through different pathways. That is, both apocynin and galantamine diminished NADPH oxidase expression, but their effects on transcription factor expression differed. Moreover, experiments in silico showed that galantamine did not interact with the active site of beta secretase, whereas diapocynin, an apocynin metabolite, interacted with the beta-site APP-cleaving enzyme (BACE1) at the catalytic site.