Farbood Yaghoob, Shabani Sahreh, Sarkaki Alireza, Mard Seyyed Ali, Ahangarpour Akram, Khorsandi Layasadat
Physiology Research Center, Department of Physiology, Medical School, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Cellular and Molecular Research Center, Department of Anatomical Sciences, Medical School, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Metab Brain Dis. 2017 Jun;32(3):693-701. doi: 10.1007/s11011-016-9947-2. Epub 2017 Jan 26.
The amyloid beta (Aβ) induced Alzheimer's disease (AD) is associated with formation the amyloid plaques, cognitive impairments and decline in spontaneous discharge of neurons. In the current study, we evaluated the effect of subcutaneous (S. C) and intrahippocampal (I. H) administrations of triiodothyronine (T3) on the histological changes, memory and the dentate gyrus (DG) electrophysiological activity in an animal model of AD. Eighty adult male Wistar rats (250-300 g) were divided randomly into five groups: Sham-Operated (Sh-O), AD + Vehicle (S. C), AD + Vehicle (I. H), AD+ T3 (S. C) and AD + T3 (I. H). In order to induce animal model of AD, Aβ (10 ng/μl, bilaterally) were injected intrahippocampally. Rats were treated with T3 and/or normal saline for 10 days. Passive avoidance and spatial memory were evaluated in shuttle box apparatus and Morris water maze, respectively. Neuronal single unit recording was assessed from hippocampal DG. The percent of total time that animals spent in target quarter, the mean latency time (sec), the step through latency and the average number of spikes/bin were decreased significantly in AD rats compared with the Sh-O group (p < 0.001) and were increased significantly in AD groups that have received T3 (S. C and I. H) in compared with AD group (p < 0.01, p < 0.001). Also, formation of amyloid plaques was decreased in AD rats treated with T3.The results showed that T3 injection (S. C and I. H), by reduction of neural damage and increment of neuronal spontaneous activity improved the memory deficits in Aβ-induced AD rats.
淀粉样蛋白β(Aβ)引发的阿尔茨海默病(AD)与淀粉样斑块的形成、认知障碍以及神经元自发放电减少有关。在本研究中,我们评估了皮下(S.C)和海马内(I.H)注射三碘甲状腺原氨酸(T3)对AD动物模型组织学变化、记忆及齿状回(DG)电生理活动的影响。80只成年雄性Wistar大鼠(250 - 300克)被随机分为五组:假手术组(Sh - O)、AD + 赋形剂(S.C)、AD + 赋形剂(I.H)、AD + T3(S.C)和AD + T3(I.H)。为诱导AD动物模型,双侧海马内注射Aβ(10纳克/微升)。大鼠接受T3和/或生理盐水治疗10天。分别在穿梭箱装置和莫里斯水迷宫中评估被动回避和空间记忆。从海马DG进行神经元单细胞记录。与Sh - O组相比,AD大鼠在目标象限花费的总时间百分比、平均潜伏期时间(秒)、穿通潜伏期和平均每bin峰数显著降低(p < 0.001),与AD组相比,接受T3(S.C和I.H)的AD组上述指标显著增加(p < 0.01,p < 0.001)。此外,用T3治疗的AD大鼠淀粉样斑块形成减少。结果表明,T3注射(S.C和I.H)通过减少神经损伤和增加神经元自发活动改善了Aβ诱导的AD大鼠的记忆缺陷。