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

Article type: Research Article

Authors: Segura-Uribe, Julia J.^{a; *} | García-de la Torre, Paola^b | Castillo-Mendieta, Tzayaka^c | Bribiesca-Cruz, Iván^c | Orozco-Suárez, Sandra^b | Soriano-Ursúa, Marvin A.^d | Pinto-Almazán, Rodolfo^d | Fuentes-Venado, Claudia E.^e | Guerra-Araiza, Christian^{c; *}

Affiliations: [a] Subdirección de Gestión de la Investigación, Hospital Infantil de Mexico Federico Gómez, Secretarya de Salud, Mexico City, Mexico | [b] Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico | [c] Unidad de Investigación Médica en Farmacologya, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico | [d] Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico | [e] Servicio de Medicina Física y Rehabilitación, Hospital General de Zona No 197, Texcoco, State of Mexico, Mexico

Correspondence: [*] Correspondence to: Christian Guerra-Araiza, Unidad de Investigación Mídica en Enfermedades Neurológicas, Hospital de Especialidades, Centro Mídico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtímoc 330, Doctores, Cuauhtímoc, 06720, Mexico City, Mexico. Tel.:+52 1 55 56 27 69 00; E-mail: [email protected]. and Julia J. Segura-Uribe, Subdirección de Gestión de la Investigación, Hospital Infantil de México Federico Gómez, Secretaría de Salud, Dr. Márquez 162, Cuauhtémoc, 06720, Mexico City, Mexico. Tel.:+52 1 55 83 30 89 24; E-mail: [email protected].

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 Aβ40 and Aβ42 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 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.

Keywords: Hippocampus, hormone replacement therapy, menopause, neuroprotection, meta-analysis

DOI: 10.3233/JAD-220434

Journal: Journal of Alzheimer's Disease, vol. 90, no. 4, pp. 1437-1447, 2022