Student Research Committee, Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Drug Chem Toxicol. 2020 Jan;43(1):57-63. doi: 10.1080/01480545.2018.1481085. Epub 2018 Jun 21.
The effect of levothyroxine (L-T4) on the learning and memory impairment induced by streptozotocin (STZ) and brain tissue oxidative damage in rats was evaluated. An animal model of the Alzheimer's disease (AD) was established by intracerebroventricular injection of STZ (3 mg/kg) in male Wistar rats (250 ± 50 g). After that, the rats were treated for 3 weeks with L-T4 (10, 100 μg/kg) or normal saline. Passive avoidance (PA) learning and spatial memory were evaluated using shuttle box and Morris water maze (MWM), respectively. Finally, the rats were euthanized, their blood samples were collected for further thyroxine assessment and their brains were removed after decapitation in order to measure the oxidative stress parameters and brain-derived neurotrophic factor (BDNF). In the MWM, latency (s) increased in the AD rats compared with the normal control group while it decreased in the 10 μg/kg L-T4 injected AD rats compared with the AD group. In the PA, the latency for entering the dark compartment was lower in the AD group than in the normal control group and it decreased in the 10 μg/kg L-T4 injected AD rats. The low dose of L-T4 (10 μg/kg) reduced malondialdehyde concentration but increased thiols concentration, superoxide dismutase, catalase activities and BDNF level in hippocampal tissues of the AD rats. Injection of L-T4 (10 μg/kg) alleviated memory deficits and also improved factors of oxidative stress and BDNF level in the STZ-induced AD rats.
评价了左甲状腺素（L-T4）对链脲佐菌素（STZ）诱导的学习和记忆障碍以及大鼠脑组织氧化损伤的影响。通过向雄性 Wistar 大鼠（250±50g）脑室内注射 STZ（3mg/kg）建立阿尔茨海默病（AD）动物模型。之后，大鼠用 L-T4（10、100μg/kg）或生理盐水处理 3 周。使用穿梭箱和 Morris 水迷宫（MWM）分别评估被动回避（PA）学习和空间记忆。最后，大鼠安乐死后，采集血液样本进一步评估甲状腺素，断头后取出大脑，以测量氧化应激参数和脑源性神经营养因子（BDNF）。在 MWM 中，AD 大鼠的潜伏期（s）较正常对照组增加，而 10μg/kg L-T4 注射的 AD 大鼠较 AD 组减少。在 PA 中，AD 组进入暗室的潜伏期低于正常对照组，10μg/kg L-T4 注射的 AD 大鼠的潜伏期降低。低剂量 L-T4（10μg/kg）降低了丙二醛浓度，但增加了海马组织中巯基、超氧化物歧化酶、过氧化氢酶活性和 BDNF 水平。L-T4（10μg/kg）的注射缓解了记忆障碍，还改善了 STZ 诱导的 AD 大鼠的氧化应激和 BDNF 水平。
