Prieto-Almeida Fernanda, Panveloski-Costa Ana Carolina, Crunfli Fernanda, da Silva Teixeira Silvania, Nunes Maria Tereza, Torrão Andréa da Silva
Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, 05508-000 São Paulo, SP, Brazil.
Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, 05508-000 São Paulo, SP, Brazil.
Life Sci. 2018 Jan 1;192:253-258. doi: 10.1016/j.lfs.2017.11.013. Epub 2017 Nov 11.
Diabetes mellitus (DM) and impairments of glucose metabolism and insulin resistance in the brain have been suggested as a likely etiology of Alzheimer's disease (AD). Studies have shown that thyroid hormones (THs) improve insulin sensitivity in DM rats and act as mediators of the plasticity of the nervous system altering behavior and cognitive function. Based on these findings, this study aimed to evaluate the effects of diabetes and triiodothyronine (T3) treatment upon proteins associated with DM and AD in the central nervous system.
Euglycemic and Diabetic (alloxan-induced) male Wistar rats were daily treated with T3 (1.5μg/100g body weight) or vehicle (saline) for a 4-week period and subdivided into the following groups: euglycemic treated with saline (Control=C); diabetic treated with saline (Diabetic=D); euglycemic treated with T3 (T3); diabetic treated with T3 (DT3). The expression of insulin signaling, neurodegenerative and neuron survival markers was evaluated in the hippocampus by immunoblotting, ELISA, and RT-PCR.
T3 treatment decreased glycemia, restored the insulin signaling and reduced the activation of glycogen synthase kinase 3 (GSK3) and tau proteins content in the hippocampus of diabetic rats.
The present data provide evidence that T3 treatment of diabetic rats is able to improve insulin sensitivity and reduce the activation of the neurodegenerative pathway in the brain, which might provide neuroprotection in this experimental model.
糖尿病（DM）以及大脑中葡萄糖代谢受损和胰岛素抵抗被认为可能是阿尔茨海默病（AD）的病因。研究表明，甲状腺激素（THs）可提高糖尿病大鼠的胰岛素敏感性，并作为神经系统可塑性的介质，改变行为和认知功能。基于这些发现，本研究旨在评估糖尿病和三碘甲状腺原氨酸（T3）治疗对中枢神经系统中与糖尿病和阿尔茨海默病相关蛋白质的影响。
对血糖正常和糖尿病（用四氧嘧啶诱导）的雄性Wistar大鼠每天给予T3（1.5μg/100g体重）或溶剂（生理盐水），持续4周，并分为以下几组：用生理盐水治疗的血糖正常组（对照组=C）；用生理盐水治疗的糖尿病组（糖尿病组=D）；用T3治疗的血糖正常组（T3组）；用T3治疗的糖尿病组（DT3组）。通过免疫印迹、酶联免疫吸附测定和逆转录聚合酶链反应评估海马体中胰岛素信号、神经退行性变和神经元存活标志物的表达。
T3治疗可降低糖尿病大鼠的血糖水平，恢复胰岛素信号，并降低糖原合酶激酶3（GSK3）的活性以及海马体中tau蛋白的含量。
目前的数据表明，T3治疗糖尿病大鼠能够提高胰岛素敏感性，并减少大脑中神经退行性变途径的激活，这可能在该实验模型中提供神经保护作用。
