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脂多糖诱导的 Na/K-ATP 酶活性损伤:鞣酸对小鼠的改善作用。

LPS-induced impairment of Na/K-ATPase activity: ameliorative effect of tannic acid in mice.

机构信息

Programa de Pós-Graduação em Bioquímica e Bioprospecção, Laboratório de Biomarcadores, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário s/n, Pelotas, RS, CEP: 96010-900, Brazil.

Programa de Pós-Graduação em Bioquímica e Bioprospecção, Laboratório de Neuroquímica, Inflamação e Câncer, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário s/n, Pelotas, RS, CEP: 96010-900, Brazil.

出版信息

Metab Brain Dis. 2022 Aug;37(6):2133-2140. doi: 10.1007/s11011-022-01036-y. Epub 2022 Jun 27.

DOI:10.1007/s11011-022-01036-y
PMID:35759073
Abstract

Acetylcholine is an excitatory neurotransmitter that modulates synaptic plasticity and communication, and it is essential for learning and memory processes. This neurotransmitter is hydrolyzed by acetylcholinesterase (AChE), which plays other cellular roles in processes such as inflammation and oxidative stress. Ion pumps, such as Na/K-ATPase and Ca-ATPase, are highly expressed channels that derive energy for their functions from ATP hydrolysis. Impairment of the cholinergic system and ion pumps is associated with neuropsychiatric diseases. Major depressive disorder (MDD) is an example of a complex disease with high morbidity and a heterogenous etiology. Polyphenols have been investigated for their therapeutic effects, and tannic acid (TA) has been reported to show neuroprotective and antidepressant-like activities. Animal models of depression-like behavior, such as lipopolysaccharide (LPS)-induced models of depression, are useful for investigating the pathophysiology of MDD. In this context, effects of TA were evaluated in an LPS-induced mouse model of depression-like behavior. Animals received TA for 7 days, and on the last day of treatment, LPS (830 μg/kg) was administered intraperitoneally. In vitro exposure of healthy brain to TA decreased the AChE activity. Additionally, this enzyme activity was decreased in cerebral cortex of LPS-treated mice. LPS injection increased the activity of Ca-ATPase in the cerebral cortex but decreased the enzyme activity in the hippocampus. LPS administration decreased Na/K-ATPase activity in the cerebral cortex, hippocampus, and striatum; however, TA administration prevented these changes. In conclusion, tannins may affect Na/K-ATPase and Ca-ATPase activities, which is interesting in the context of MDD.

摘要

乙酰胆碱是一种兴奋性神经递质,可调节突触可塑性和通讯,对学习和记忆过程至关重要。这种神经递质被乙酰胆碱酯酶(AChE)水解,AChE 在炎症和氧化应激等过程中发挥其他细胞作用。离子泵,如 Na/K-ATP 酶和 Ca-ATP 酶,是高度表达的通道,其功能所需的能量来自 ATP 水解。胆碱能系统和离子泵的损伤与神经精神疾病有关。重度抑郁症(MDD)是一种发病率高且病因异质性的复杂疾病的例子。多酚已被研究其治疗效果,单宁酸(TA)已被报道具有神经保护和抗抑郁样活性。抑郁样行为的动物模型,如脂多糖(LPS)诱导的抑郁模型,可用于研究 MDD 的病理生理学。在这种情况下,评估了 TA 在 LPS 诱导的抑郁样行为小鼠模型中的作用。动物接受 TA 治疗 7 天,在治疗的最后一天,腹膜内注射 LPS(830μg/kg)。健康大脑体外暴露于 TA 会降低 AChE 活性。此外,LPS 处理的小鼠大脑皮质中的这种酶活性降低。LPS 注射增加了大脑皮质中 Ca-ATP 酶的活性,但降低了海马中的酶活性。LPS 给药降低了大脑皮质、海马体和纹状体中的 Na/K-ATP 酶活性;然而,TA 给药可预防这些变化。总之,单宁可能会影响 Na/K-ATP 酶和 Ca-ATP 酶的活性,这在 MDD 方面很有趣。

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