Tibolone Improves Memory and Decreases the Content of Amyloid-ß Peptides and Tau Protein in the Hippocampus of a Murine Model of Alzheimer's Disease.

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 Aß 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 Aß40 and Aß42 and phosphorylated and total tau.ResultsA 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 Aß 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.

Validation of housekeeping genes as an internal control for gene expression studies in the brain of ovariectomized rats treated with tibolone.

INTRODUCTION: In the central nervous system (CNS), tibolone actions are mainly modulated through its interaction with estrogen, progesterone, and androgen receptors. Several studies have reported the expression of sex hormone receptors in the CNS using the RT-PCR endpoint technique. Although some studies have validated reference genes for rat brain tissue in different experimental conditions, no suitable reference genes have been reported in brain tissue from ovariectomized rats treated with tibolone. OBJECTIVE: The aim of this investigation was to evaluate the expression of different housekeeping genes in several brain regions in ovariectomized rats treated with tibolone to determine the stability of a single housekeeping gene and a combination of two housekeeping genes under these experimental conditions. METHODS: Adult female Sprague-Dawley rats were ovariectomized. Seven days after the surgery, animals were administered a single dose of vehicle (water) or tibolone (10 mg/kg/weight). Twenty-four hours later, animals were sacrificed, and the hypothalamus, hippocampus, prefrontal cortex, and cerebellum were dissected. Total RNA was extracted from these tissues, and RT-qPCR was performed to amplify Ppia, Hprt1, Rpl32, and Gapdh housekeeping genes. RESULTS: Ppia was the most stable gene in the hypothalamus and cerebellum, whereas Hprt1 was the most stable gene in the prefrontal cortex. For the analysis of the combination of two genes, the most stable combination was Ppia and Hrpt1 for the prefrontal cortex and Ppia and Rpl32 for the cerebellum. CONCLUSION: In ovariectomized rats treated with tibolone, Hprt1 and Ppia genes showed high stability as housekeeping genes for qPCR analysis.

Maqui berry (Aristotelia chilensis) extract improves memory and decreases oxidative stress in male rat brain exposed to ozone.

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.