Amelioration of Repeated Restraint Stress-Induced Behavioral Deficits and Hippocampal Anomalies with Taurine Treatment in Mice

Amelioration of Repeated Restraint Stress-Induced Behavioral Deficits and Hippocampal Anomalies with Taurine Treatment in Mice
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DOI:
10.1007/s11064-019-02945-8
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发表时间:
2020-01-02
影响因子:
4.4
通讯作者:
Lahkar, Mangala
Lahkar, Mangala
中科院分区:
医学3区
文献类型:
--
作者:
Jangra, Ashok;Rajput, Prabha;Lahkar, Mangala

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牛磺酸是一种重要的中性食品,已被报道具有抗氧化和抗炎特性。大量证据表明,长期的压力是导致心理和生理异常的主要原因之一。束缚应激大鼠模型是目前应用最广泛的慢性心理情绪应激诱导的实验模型。在本研究中,瑞士白化雄性小鼠被束缚6小时/天,连续28天。动物分为4组:对照组、RS组、RS+牛磺酸组和牛磺酸对照组。牛磺酸是一种有效的抗氧化剂,在RS的同时口服(200 mg/kg),共28天。牛磺酸干预可明显恢复RS诱导的神经行为改变,表现为高架正迷宫、Morris水迷宫试验、强迫游泳试验、悬尾试验和蔗糖偏好试验。此外,牛磺酸显著防止了海马区氧化应激(脂质过氧化、还原型谷胱甘肽和亚硝酸盐)和其他神经化学(乙酰胆碱酯酶和IL-1β)异常。通过Western blotting分析,我们证明牛磺酸治疗显著改善了海马区脑源性神经营养因子、caspase-3和核因子-kappa轻链增强因子(nf-kappaB)水平的变化。因此,牛磺酸通过抑制核因子-kappa B信号通路有效地抑制RS诱导的氧化应激、神经炎症和细胞凋亡。综上所述,我们的研究首次证明了核因子-kappa B和半胱氨酸天冬氨酸氨基转移酶-3的抑制,以及BDNF的增强,参与了牛磺酸对RS诱导的行为异常的神经保护作用。
Taurine, an essential neutraceutical, has been reported to exhibit antioxidant and anti-inflammatory properties. Substantial evidence indicates that prolonged stress is one of the leading causes of psychological and physiological anomalies. Restraint stress (RS) rat model is the most widely used experimental model for the induction of chronic psycho-emotional stress. In the present study, Swiss albino male mice were restrained for 6 h/day for 28 consecutive days. Animals were divided into four groups: control, RS, RS + taurine, and taurine control group. Taurine, a potent antioxidant, was administered (200 mg/kg) orally along with RS for 28 days. The taurine intervention significantly restored the RS-induced neurobehavioral alterations evident by the elevated plus-maze, Morris water maze test, forced swim test, tail suspension test, and a sucrose preference test. Moreover, taurine significantly prevented hippocampal oxidative stress (lipid peroxidation, reduced glutathione, and nitrite) and other neurochemical (acetylcholinesterase, and IL-1 beta) anomalies. Using western blotting analyses, we demonstrate that taurine treatment significantly ameliorated the alterations in Brain-derived neurotrophic factor, caspase-3, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) level in the hippocampus. Thus, Taurine effectively inhibited RS-induced oxidative stress, neuroinflammation, and apoptosis via a mechanism involving the inhibition of the NF-kappa B signaling pathway. In summary, our study is the first to demonstrate that NF-kappa B and caspase-3 inhibition, as well as BDNF augmentation, was involved in neuroprotective potential of taurine against RS-induced behavioural anomalies.