Maglione Andréa V, do Nascimento Bruna P P, Ribeiro Miriam O, de Souza Talytha J L, da Silva Renata E C, Sato Monica A, Penatti Carlos A A, Britto Luiz R G, de Souza Janaina S, Maciel Rui M B, da Conceição Rodrigo Rodrigues, Laureano-Melo Roberto, Giannocco Gisele
Dept. Medicine, Laboratory of Endocrinology and Translational Medicine, Universidade Federal de São Paulo, UNIFESP/EPM, São Paulo, Brazil.
Laboratory of Translational Medicine, Universidade Federal de São Paulo, UNIFESP/EPM, São Paulo, Brazil.
Metab Brain Dis. 2022 Dec;37(8):2735-2750. doi: 10.1007/s11011-022-01055-9. Epub 2022 Aug 11.
Alzheimer disease's (AD) is a neurodegenerative disorder characterized by cognitive and behavioral impairment. The central nervous system is an important target of thyroid hormones (TH). An inverse association between serum triiodothyronine (T3) levels and the risk of AD symptoms and progression has been reported. We investigated the effects of T3 treatment on the depression-like behavior in male transgenic 3xTg-AD mice. Animals were divided into 2 groups treated with daily intraperitoneal injections of 20 ng/g of body weight (b.w.) L-T3 (T3 group) or saline (vehicle, control group). The experimental protocol lasted 21 days, and behavioral tests were conducted on days 18-20. At the end of the experiment, the TH profile and hippocampal gene expression were evaluated. The T3-treated group significantly increased serum T3 and decreased thyroxine (T4) levels. When compared to control hippocampal samples, the T3 group exhibited attenuated glycogen synthase kinase-3 (GSK3), metalloproteinase 10 (ADAM10), amyloid-beta precursor-protein (APP), serotonin transporter (SERT), 5HT1A receptor, monocarboxylate transporter 8 (MCT8) and bone morphogenetic protein 7 (BMP-7) gene expression, whereas augmented superoxide dismutase 2 (SOD2) and Hairless gene expression. T3-treated animals also displayed reduced immobility time in both the tail suspension and forced swim tests, and in the latter presented a higher latency time compared to the control group. Therefore, our findings suggest that in an AD mouse model, T3 supplementation promotes improvements in depression-like behavior, through the modulation of the serotonergic related genes involved in the transmission mediated by 5HT1A receptors and serotonin reuptake, and attenuated disease progression.
阿尔茨海默病（AD）是一种以认知和行为障碍为特征的神经退行性疾病。中枢神经系统是甲状腺激素（TH）的重要作用靶点。已有报道称血清三碘甲状腺原氨酸（T3）水平与AD症状及进展风险呈负相关。我们研究了T3治疗对雄性转基因3xTg-AD小鼠抑郁样行为的影响。将动物分为两组，分别每日腹腔注射20 ng/g体重的L-T3（T3组）或生理盐水（溶剂对照组）。实验方案持续21天，在第18 - 20天进行行为测试。实验结束时，评估甲状腺激素谱和海马基因表达。T3治疗组血清T3显著升高，甲状腺素（T4）水平降低。与对照海马样本相比，T3组糖原合酶激酶-3（GSK3）、金属蛋白酶10（ADAM10）、淀粉样前体蛋白（APP）、5-羟色胺转运体（SERT）、5HT1A受体、单羧酸转运体8（MCT8）和骨形态发生蛋白7（BMP-7）基因表达减弱，而超氧化物歧化酶2（SOD2）和无毛基因表达增强。T3治疗的动物在悬尾试验和强迫游泳试验中的不动时间也减少，且在强迫游泳试验中与对照组相比潜伏期更长。因此，我们的研究结果表明，在AD小鼠模型中，补充T3可通过调节与5HT1A受体介导的传递及5-羟色胺再摄取相关的血清素能相关基因，促进抑郁样行为的改善，并减缓疾病进展。
