Faculty of Life Science and Biotechnology, Kunming University of Science and Technology, Kunming, 650500, China.
Department of Medical Genetics, NHC Key Laboratory of Preconception Health Birth in Western China, Yunnan Provincial Key Laboratory for Birth Defects and Genetic Diseases, Yunnan Provincial Clinical Research Center for Birth Defects and Rare Diseases, The Affiliated Hospital of Kunming University of Science and Technology, The First People's Hospital of Yunnan Province, Kunming, 650032, China.
Mol Neurobiol. 2024 Apr;61(4):2390-2410. doi: 10.1007/s12035-023-03665-5. Epub 2023 Oct 25.
The human fetal thyroid gland is not capable of producing thyroid hormones independently until 20 weeks of gestation, and if maternal thyroid hormone synthesis is inadequate in early pregnancy, fetal brain and nerve development may be affected by maternal hypothyroidism. Curcumin, which is isolated from turmeric (Curcuma longa), has been shown to be effective in repairing neurological disorders and is effective in relieving nerve damage when consumed over a long period of time. In this experiment, we investigated the effect of curcumin supplementation on synaptic development of rat hippocampal neurons. A cell model of oxidative damage and a young rat model of hypothyroidism were constructed, and model cells and rats were treated with triiodothyronine (T3), tetraiodothyronine (T4), and curcumin, respectively. Damage of nerve cells and animal brain tissues was examined, and the effect of curcumin in alleviating the blocked neurodevelopment was investigated. Further modulation of GSK-3β/β-catenin was performed to investigate the mechanism of action of curcumin. Ultimately, we found that T3-, T4-, and curcumin-treated model cells and young rats had increased numbers of synapses and good neurodevelopment. At the same time, we found that curcumin inhibited the production of GSK-3β and Axin to activate β-catenin. The inhibition of β-catenin weakened the therapeutic effect of curcumin, and the differences between the indicators and the model group disappeared. Both cellular and animal experiments supported that curcumin effectively alleviated the oxidative cell damage caused by thyroxine deficiency and activated the synaptogenic ability of nerve synapses by inhibiting GSK-3β and protecting β-catenin activity.
人类胎儿的甲状腺在妊娠 20 周之前无法独立产生甲状腺激素，如果母亲在妊娠早期甲状腺激素合成不足，可能会影响胎儿的大脑和神经发育。姜黄素是从姜黄（Curcuma longa）中分离出来的，已被证明对修复神经紊乱有效，并且在长期摄入时对缓解神经损伤有效。在这项实验中，我们研究了姜黄素补充对大鼠海马神经元突触发育的影响。构建了氧化损伤细胞模型和甲状腺功能减退的幼鼠模型，并分别用三碘甲状腺原氨酸（T3）、四碘甲状腺原氨酸（T4）和姜黄素处理模型细胞和大鼠。检查神经细胞和动物脑组织的损伤，并研究姜黄素缓解神经发育受阻的作用。进一步对 GSK-3β/β-catenin 进行了调制，以研究姜黄素的作用机制。最终，我们发现 T3、T4 和姜黄素处理的模型细胞和幼鼠的突触数量增加，神经发育良好。同时，我们发现姜黄素抑制 GSK-3β 和 Axin 的产生以激活β-catenin。β-catenin 的抑制削弱了姜黄素的治疗效果，并且指标与模型组之间的差异消失。细胞和动物实验均支持姜黄素通过抑制 GSK-3β 并保护β-catenin 活性，有效缓解甲状腺素缺乏引起的氧化细胞损伤，并激活神经突触的突触形成能力。
