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Gonadal hormones regulate expression and activation of protein tau. Tibolone is a drug used as first- choice comprehensive treatment for the relief of menopausal symptoms, because it and its various metabolites have estrogenic properties and progestogenic/androgenic effects; however, the effect on the activation of tau protein and its signaling cascade in the brain is unknown. We studied the effect of chronic administration of estradiol (E2), progesterone (P4), and tibolone (TIB) on the expression and phosphorylation of microtubule-associated protein tau and glycogen synthase kinase-3β (GSK3β) in the hippocampus and cerebellum of ovariectomized rats. Ovariectomized adult female rats were implanted with pellets of vehicle, E2, or P4 or were treated with TIB by oral administration for 60 days. The animals were sacrificed, and tissue proteins were analyzed by Western blot. We observed that, in the hippocampus, administration of E2, P4, or TIB significantly decreased the protein content of hyperphosphorylated tau and increased the tau dephosphorylated form, whereas only treatment with TIB increased the content of the phosphorylated form of GSK3β. In the cerebellum, E2 and TIB treatments resulted in a significant decrease in the expression of hyperphosphorylated tau, whereas E2 and TIB increased phosphorylated GSK3β; P4 had no effect. These results indicate that chronic administration of gonadal hormones and tibolone modulates tau and GSK3β phosphorylation in hippocampus and cerebellum of the rat and may exert a neuroprotective effect in these tissues., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: Alzheimer's disease (AD) affects women more than men and consequently has been associated with menopause. Tibolone (TIB) has been used as a hormone replacement therapy to alleviate climacteric symptoms. Neuroprotective effects of TIB have also been reported in some animal models. Objective: This study aimed to assess the effect of TIB on memory and Aβ peptides and tau protein content in the hippocampus and cerebellum of transgenic 3xTgAD ovariectomized mice. Methods: Three-month-old female mice were ovariectomized. Ten days after surgery, animals were divided into four groups: wild-type (WT)+vehicle; WT+TIB (1 mg/kg); 3xTgAD+vehicle; and 3xTgAD+TIB (1 mg/kg). TIB was administered for three months, and memory was evaluated using the object-in-context recognition task. Subsequently, animals were decapitated, and the hippocampus and cerebellum were dissected. Using commercial ELISA kits, these brain structures were homogenized in a PBS buffer for quantifying Aβ40 and Aβ42 and phosphorylated and total tau. Results: A long-term memory deficit was observed in the 3xTgAD+vehicle group. In contrast, TIB treatment improved long-term memory in the 3xTgAD+TIB group than those treated with vehicle (p < 0.05). Furthermore, TIB treatment decreased Aβ and tau content in the hippocampus of 3xTgAD mice compared to vehicle-treated groups (p < 0.05). No significant changes were observed in the cerebellum. Conclusion: Chronic treatment with TIB showed neuroprotective effects and delayed AD neuropathology in the 3xTgAD mice. Our results support hormone replacement therapy with TIB in menopausal women for neuroprotection. [ABSTRACT FROM AUTHOR]

Introduction: Prolonged ozone exposure can produce a state of oxidative stress, which in turn causes alterations in the dynamics of the brain and affects memory and learning. Moreover, different investigations have shown that high flavonoid content berries show a great antioxidant activity. The relationship between the protective effect of the maqui berry extract and its antioxidant properties in the brain has not been studied in depth. Objectives: The present study evaluated whether the protection exerted by the aqueous extract of maqui berry in brain regions associated with cognitive performance is due to its antioxidant capacity. Methods: Sprague Dawley rats were exposed to 0.25 ppm ozone and administered with maqui berry extracts. At the end of the treatments, spatial learning and short- and long-term memory were evaluated, as well as oxidative stress markers. Results: The administration of 50 and 100 mg/kg of the aqueous extract of maqui berry was effective in preventing the cognitive deficit caused by chronic exposure to ozone. The antioxidant effect of the administration of maqui berry was analyzed in the prefrontal cortex, hippocampus, and amygdala. Oxidative stress markers levels decreased and the enzymatic activity of superoxide dismutase diminished in animals exposed to ozone treated with the 50 mg/kg dose of maqui berry. Discussion: These results show a relationship between protection at the cognitive level and a decrease in oxidative stress markers, which suggests that the prevention of cognitive damage is due to the antioxidant activity of the maqui berry. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]