TY - JOUR
T1 - 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
AU - Segura-Uribe, Julia J.
AU - García-De La Torre, Paola
AU - Castillo-Mendieta, Tzayaka
AU - Bribiesca-Cruz, Iván
AU - Orozco-Suárez, Sandra
AU - Soriano-Ursúa, Marvin A.
AU - Pinto-Almazán, Rodolfo
AU - Fuentes-Venado, Claudia E.
AU - Guerra-Araiza, Christian
N1 - Publisher Copyright:
© 2022 - IOS Press. All rights reserved.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Hippocampus
KW - hormone replacement therapy
KW - menopause
KW - meta-analysis
KW - neuroprotection
UR - http://www.scopus.com/inward/record.url?scp=85143916972&partnerID=8YFLogxK
U2 - 10.3233/JAD-220434
DO - 10.3233/JAD-220434
M3 - Artículo
C2 - 36278346
AN - SCOPUS:85143916972
SN - 1387-2877
VL - 90
SP - 1437
EP - 1447
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 4
ER -