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Neuronal Nitric Oxide Inhibitor 7-Nitroindazole Improved Brain-Derived Neurotrophic Factor and Attenuated Brain Tissues Oxidative Damage and Learning and Memory Impairments of Hypothyroid Juvenile Rats.
Neurochemical Research ( IF 4.4 ) Pub Date : 2020-09-15 , DOI: 10.1007/s11064-020-03128-6
Sara Memarpour 1 , Farimah Beheshti 2, 3 , Yousef Baghcheghi 4 , Abbas Ali Vafaei 1 , Mahmoud Hosseini 5 , Ali Rashidy-Pour 1
Affiliation  

Hypothyroidism-associated learning and memory impairment is reported to be connected to oxidative stress and reduced levels of brain-derived neurotrophic factor (BDNF). The effects of neuronal nitric oxide inhibitor 7-nitroindazole (7NI) on brain tissues oxidative damage, nitric oxide (NO), BDNF and memory impairments in hypothyroid juvenile rats were investigated. Male Wistar juvenile rats (20 days old) were divided into five groups, including Martinez et al. (J Neurochem 78 (5):1054–1063, 2001). Control in which vehicle was injected instead of 7NI, (Jackson in Thyroid 8 (10):951–956, 1998) Propylthiouracil (PTU) where 0.05% PTU was added in drinking water and vehicle was injected instead of 7NI, (Gong et al. in BMC Neurosci 11 (1):50, 2010; Alva-Sánchez et al. in Brain Res 1271:27–35, 2009; Anaeigoudari et al. in Pharmacol Rep 68 (2): 243–249, 2016) PTU-7NI 5, PTU-7NI 10 and PTU-7NI 20 in which 5, 10, or 20 mg/kg7NI was injected intraperitoneally (i.p.). Following 6 weeks, Morris water maze (MMW) and passive avoidance learning (PAL) tests were used to evaluate the memory. Finally, the hippocampus and the cortex of the rats were removed after anesthesia by urethane to be used for future analysis. The escape latency and traveled path in MWM test was increased in PTU group (P < 0.001). PTU also reduced the latency to enter the dark box of PAL and the time spent and the distance in the target quadrant in MWM test (P < 0.001 and P < 0.01). Treatment with 7NI attenuated all adverse effects of PTU (P < 0.05 to P < 0.001). PTU lowered BDNF and thiol content and superoxide dismutase (SOD) and catalase (CAT) activities in the brain but increased malondialdehyde (MDA) and nitric oxide (NO) metabolites. In addition, 7NI improved thiol, SOD, CAT, thiol, and BDNF but attenuated MDA and NO metabolites. The results of the current study showed that 7NI improvement in the learning and memory of the hypothyroid juvenile rats, which was accompanied with improving of BDNF and attenuation of NO and brain tissues oxidative damage.



中文翻译:

神经元一氧化氮抑制剂 7-硝基吲唑改善脑源性神经营养因子并减轻脑组织氧化损伤以及甲状腺功能减退幼鼠的学习和记忆障碍。

据报道,甲状腺功能减退症相关的学习和记忆障碍与氧化应激和脑源性神经营养因子 (BDNF) 水平降低有关。研究了神经元一氧化氮抑制剂7-硝基吲唑(7NI)对甲状腺功能减退幼鼠脑组织氧化损伤、一氧化氮(NO)、BDNF和记忆障碍的影响。雄性 Wistar 幼鼠(20 天大)被分为五组,包括 Martinez 等人。(J Neurochem 78 (5):1054–1063, 2001)。注射载体而不是 7NI 的对照,(Jackson in Thyroid 8 (10):951–956, 1998)丙硫氧嘧啶 (PTU),其中在饮用水中添加 0.05% PTU 并注射载体而不是 7NI,(Gong 等人. 在 BMC Neurosci 11 (1):50, 2010;Alva-Sánchez 等人在 Brain Res 1271:27–35, 2009;Anaeigoudari 等人在 Pharmacol Rep 68 (2):243–249,2016) PTU-7NI 5、PTU-7NI 10 和 PTU-7NI 20,其中腹膜内 (ip) 注射 5、10 或 20 mg/kg7NI。6 周后,使用莫里斯水迷宫 (MMW) 和被动回避学习 (PAL) 测试来评估记忆。最后,用氨基甲酸乙酯麻醉后取出大鼠的海马和皮质,以供将来分析。PTU组MWM测试中的逃逸潜伏期和行进路径增加(P < 0.001)。PTU 还减少了进入 PAL 暗箱的延迟以及在 MWM 测试中花费的时间和在目标象限中的距离(P < 0.001 和 P < 0.01)。7NI 治疗减轻了 PTU 的所有不良反应(P < 0.05 至 P < 0.001)。PTU 降低了大脑中的 BDNF 和硫醇含量以及超氧化物歧化酶 (SOD) 和过氧化氢酶 (CAT) 活性,但增加了丙二醛 (MDA) 和一氧化氮 (NO) 代谢物。此外,7NI 改善了硫醇、SOD、CAT、硫醇和 BDNF,但减弱了 MDA 和 NO 代谢物。本研究结果表明,7NI对甲状腺功能减退幼鼠的学习记忆有改善作用,同时伴有BDNF的改善和NO和脑组织氧化损伤的减弱。

更新日期:2020-09-15
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