1. Tibolone Improves Memory and Decreases the Content of Amyloid-β Peptides and Tau Protein in the Hippocampus of a Murine Model of Alzheimer's Disease.
- Author
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Segura-Uribe, Julia J., García-de la Torre, Paola, Castillo-Mendieta, Tzayaka, Bribiesca-Cruz, Iván, Orozco-Suárez, Sandra, Soriano-Ursúa, Marvin A., Pinto-Almazán, Rodolfo, Fuentes-Venado, Claudia E., and Guerra-Araiza, Christian
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ALZHEIMER'S disease ,TAU proteins ,HIPPOCAMPUS (Brain) ,LONG-term memory ,MEMORY disorders ,PEPTIDES ,RECOGNITION (Psychology) - Abstract
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 Aβ
40 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]- Published
- 2022
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