Learning and Motivation ( IF 1.488 ) Pub Date : 2020-07-16 , DOI: 10.1016/j.lmot.2020.101654 Mohammad Ali Mirshekar , Halimeh Lakzaei , Sahreh Shabani
Scopolamine (SCOP), an anticholinergic drug, is commonly used for inducing a cognitive deficiency in experimental animal models. Ninety six Wistar male rats were divided into six groups [Control, Control + Levothyroxine (L-T4, 100), SCOP + Vehicle, SCOP + L-T4 (50 and 100), SCOP + donepezil (DP)]. During 21 consecutive days, SCOP (1 mg/kg, i.p.) was used with the purpose of inducing an animal model of cognitive impairment. Thirty min after the administration of SCOP, animals were treated with 50 and 100 mg/kg L-T4, 3 mg/kg of DP, or normal saline for 21 days. The behavioral (passive avoidance and spatial memory, anxiety, depression, locomotion, and motor coordination), and electrophysiological (hippocampal long-term potentiation (LTP)) assessments, as well as biochemical changes, were estimated.
Results indicated that the indices of depression/anxiety, spatial/passive avoidance memory, motor coordination, LTP records (amplitude and slope), and antioxidant enzyme activity were significantly decreased in SCOP groups in comparison with the control. Compared to the control group, L-T4 (50 and 100 mg/kg) treated rats showed significant improvements in memory and learning deficits, anxiety, all LTP parameters, and the antioxidant enzyme concentrations. The cerebral contents of tumor necrosis factor-alpha (TNF-α) in the L-T4 and DP treated groups were significantly lower than that of the SCOP + Veh group (p < 0.01).
This research showed that the L-T4 prevented the disruption of synaptic plasticity and cognitive deficiencies induced by SCOP. The beneficial effects of L-T4 may be due to a decrease in the concentration of TNF-α and enhancement of the antioxidant content in the hippocampus.
中文翻译:
左甲状腺素对东pol碱诱发的认知障碍大鼠模型的治疗作用:电生理,行为和生化研究
东co碱(SCOP)是一种抗胆碱能药物,通常用于诱发实验动物模型中的认知缺陷。将96只Wistar雄性大鼠分成六组[对照组,对照组+左甲状腺素(L-T4,100),SCOP +媒介物,SCOP + L-T4(50和100),SCOP +多奈哌齐(DP)]。在连续21天中,使用SCOP(1 mg / kg,ip)来诱导认知障碍动物模型。给予SCOP后30分钟,用50和100 mg / kg L-T4、3 mg / kg DP或生理盐水处理动物21天。评估了行为(被动回避和空间记忆,焦虑,抑郁,运动和运动协调),电生理(海马长期增强(LTP))评估以及生化变化。
结果表明,与对照组相比,SCOP组的抑郁/焦虑,空间/被动回避记忆,运动协调,LTP记录(幅度和斜率)和抗氧化酶活性的指标均明显降低。与对照组相比,L-T4(50和100 mg / kg)治疗的大鼠在记忆力和学习障碍,焦虑,所有LTP参数以及抗氧化酶浓度方面均表现出显着改善。L-T4和DP治疗组的脑坏死因子-α(TNF-α)的脑含量显着低于SCOP + Veh组(p <0.01)。
这项研究表明,L-T4可以防止SCOP引起的突触可塑性和认知缺陷的破坏。L-T4的有益作用可能是由于TNF-α浓度的降低和海马中抗氧化剂含量的增加。