Department of Medical Biology, Faculty of Medicine, Bezmialem Vakif University, 34093, Istanbul, Turkey.
Department of Medical Biology, Faculty of Medicine, Bezmialem Vakif University, 34093, Istanbul, Turkey.
Biomed Pharmacother. 2018 Mar;99:391-401. doi: 10.1016/j.biopha.2018.01.047.
Streptozotocin (STZ), a glucosamine-nitrosourea compound, produces deficiencies in learning, memory, and cognitive functions when it was administered intracerebroventricularly (i.c.v). In molecular level, increase in neuroinflammation and oxidative stress in brain, and decrease in the number of surviving neurons are the outcomes of STZ administration. Herein, we aimed to investigate the effect of thymoquinone (TQ), an anti-inflammatory, immunomodulatory and neuroprotective agent, on STZ-induced neurodegeneration in rats. For this purpose, bilateral i.c.v. injection of STZ (3 mg/kg) was given to adult female rats on days 1 and 3. TQ (20 mg/kg/day in cornoil) was administered intragastrically to rats for 15 days starting from the 15th day of STZ injection. The Morris water maze test and passive avoidance test were applied to measure the learning and memory performance of animals. Following the behavioral tests, all of the rats were sacrificed for evaluation of molecular alterations. Rats in the STZ-TQ group showed higher performance in passive avoidance test than rats in the STZ group whose memory performance declined compared to control group. The worse memory performance in STZ group was correlated with low number of surviving neurons and high number of degenerating neurons. In addition, an increase in APOE expression and a decrease in NGF expression were observed with STZ injection. Administration of TQ reversed these STZ-triggered cognitive and molecular alterations. In the present study, we observed the neuroregenerative effects of TQ by activation of JNK protein, upregulation of mir-124, and downregulation of ERK1/2 and NOS enzymes. The same ameliorative effect of TQ was also observed in the pTau protein expression. To sum up, we can say that the healing effect of TQ on STZ induced neurodegeneration opens a new door for the development of Alzheimer's disease treatment using natural products as an adjuvant when their action mechanism was explained in detail.
链脲佐菌素（STZ）是一种氨基葡萄糖-亚硝脲化合物，当它被脑室内给药时，会导致学习、记忆和认知功能缺陷。在分子水平上，脑内神经炎症和氧化应激的增加以及存活神经元数量的减少是 STZ 给药的结果。在此，我们旨在研究胸腺醌（TQ），一种抗炎、免疫调节和神经保护剂，对大鼠 STZ 诱导的神经退行性变的影响。为此，成年雌性大鼠在第 1 天和第 3 天双侧脑室内注射 STZ（3mg/kg）。TQ（角鲨烯中的 20mg/kg/天）从 STZ 注射的第 15 天开始通过灌胃给予大鼠 15 天。Morris 水迷宫试验和被动回避试验用于测量动物的学习和记忆表现。在行为测试后，所有大鼠均被处死以评估分子变化。与对照组相比，STZ 组大鼠的记忆表现下降，而 STZ-TQ 组大鼠在被动回避试验中的表现优于 STZ 组大鼠。STZ 组大鼠较差的记忆表现与存活神经元数量减少和变性神经元数量增加有关。此外，注射 STZ 后观察到 APOE 表达增加和 NGF 表达减少。TQ 的给药逆转了这些 STZ 引发的认知和分子变化。在本研究中，我们通过激活 JNK 蛋白、上调 mir-124 和下调 ERK1/2 和 NOS 酶观察到 TQ 的神经再生作用。TQ 还观察到 pTau 蛋白表达的改善作用。总之，我们可以说，TQ 对 STZ 诱导的神经退行性变的治疗效果为使用天然产物作为佐剂治疗阿尔茨海默病开辟了新的途径，当详细解释其作用机制时。
