Castillo-Mendieta Tzayaka, Bautista-Poblet Guadalupe, Coyoy-Salgado Angélica, Castillo-García Emily L, Pinto-Almazán Rodolfo, Fuentes-Venado Claudia Erika, Neri-Gómez Teresa, Guerra-Araiza Christian
CONAHCyT-Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Mexico City C.P. 03940, Mexico.
Unidad de Investigación Médica en Farmacología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Mexico City C.P. 06720, Mexico.
Brain Sci. 2024 Sep 6;14(9):903. doi: 10.3390/brainsci14090903.
Gonadal steroids exert different effects on the central nervous system (CNS), such as preserving neuronal function and promoting neuronal survival. Estradiol, progesterone, and testosterone reduce neuronal loss in the CNS in animal models of neurodegeneration. However, hormone replacement therapy has been associated with higher rates of endometrial, prostate, and breast cancer. Tibolone (TIB), the metabolites of which show estrogenic and progestogenic effects, is an alternative to reduce this risk. However, the impact of TIB on memory and learning, as well as on choline acetyltransferase (ChAT) and tryptophan hydroxylase (TPH) levels in the hippocampus of aging males, is unknown. We administered TIB to aged C57BL/6J male mice at different doses (0.01 or 1.0 mg/kg per day for 12 weeks) and evaluated its effects on memory and learning and the content of ChAT and TPH. We assessed memory and learning with object recognition and elevated T-maze tasks. Additionally, we determined ChAT and TPH protein levels in the hippocampus by Western blotting. TIB administration increased the percentage of time spent on the novel object in the object recognition task. In addition, the latency of leaving the enclosed arm increased in both TIB groups, suggesting an improvement in fear-based learning. We also observed decreased ChAT content in the group treated with the 0.01 mg/kg TIB dose. In the case of TPH, no changes were observed with either TIB dose. These results show that long-term TIB administration improves memory without affecting locomotor activity and modulates cholinergic but not serotonergic systems in the hippocampus of aged male mice.
性腺类固醇对中枢神经系统（CNS）有不同影响，比如维持神经元功能和促进神经元存活。在神经退行性变动物模型中，雌二醇、孕酮和睾酮可减少CNS中的神经元损失。然而，激素替代疗法与子宫内膜癌、前列腺癌和乳腺癌的较高发病率相关。替勃龙（TIB）的代谢产物具有雌激素和孕激素作用，是降低这种风险的一种替代药物。然而，TIB对衰老雄性小鼠海马体中记忆和学习以及胆碱乙酰转移酶（ChAT）和色氨酸羟化酶（TPH）水平的影响尚不清楚。我们以不同剂量（每天0.01或1.0 mg/kg，持续12周）给衰老的C57BL/6J雄性小鼠施用TIB，并评估其对记忆和学习以及ChAT和TPH含量的影响。我们通过物体识别和高架T迷宫任务评估记忆和学习。此外，我们通过蛋白质印迹法测定海马体中ChAT和TPH的蛋白质水平。施用TIB增加了物体识别任务中在新物体上花费时间的百分比。此外，两个TIB组离开封闭臂的潜伏期均增加，表明基于恐惧的学习有所改善。我们还观察到，用0.01 mg/kg TIB剂量治疗的组中ChAT含量降低。对于TPH，两种TIB剂量均未观察到变化。这些结果表明，长期施用TIB可改善记忆，而不影响运动活动，并调节衰老雄性小鼠海马体中的胆碱能系统而非5-羟色胺能系统。
