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在悬尾试验中,阿魏酸的急性抗抑郁样作用涉及蛋白激酶 A(PKA)、钙调蛋白依赖性蛋白激酶 II(CaMKII)、蛋白激酶 C(PKC)、丝裂原活化蛋白激酶/细胞外信号调节激酶(MAPK/ERK)和磷酸肌醇 3-激酶(PI3K)。

Involvement of PKA, CaMKII, PKC, MAPK/ERK and PI3K in the acute antidepressant-like effect of ferulic acid in the tail suspension test.

机构信息

Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, 88040-900, SC, Brazil.

出版信息

Pharmacol Biochem Behav. 2012 Dec;103(2):181-6. doi: 10.1016/j.pbb.2012.08.020. Epub 2012 Aug 31.

DOI:10.1016/j.pbb.2012.08.020
PMID:22960128
Abstract

Ferulic acid (FA, 4-hydroxy-3-methoxycinnamic acid) is a phytochemical compound naturally present in several plants and foods that is approved as an antioxidant additive and food preservative. It exerts a beneficial action in chronic mild stress-induced depressive-like behavior and produces an acute antidepressant-like effect in the tail suspension test (TST) through the activation of the serotonergic system. This study was aimed at investigating the possible involvement of signaling pathways in the antidepressant-like effect of acute and oral administration of FA, in the TST in mice. The anti-immobility effect of orally administered FA (0.01mg/kg, p.o.) was prevented by pretreatment of mice with H-89 (1μg/site, i.c.v., an inhibitor of PKA), KN-62 (1μg/site, i.c.v., an inhibitor of CaMKII), GF109203X (5ng/site, i.c.v., an inhibitor of PKC), U0126 (5μg/site, i.c.v., an inhibitor of MAPK/ERK) or LY294002 (10nmol/site, i.c.v., an inhibitor of PI3K), all involved with neurotrophic signaling pathways. The results demonstrated that FA exerts antidepressant-like effect in the TST in mice, through the activation of signaling pathways related to neuroplasticity, neurogenesis and cell survival.

摘要

阿魏酸(FA,4-羟基-3-甲氧基肉桂酸)是一种天然存在于多种植物和食物中的植物化学化合物,被批准为抗氧化剂添加剂和食品防腐剂。它通过激活 5-羟色胺能系统对慢性轻度应激诱导的抑郁样行为发挥有益作用,并在悬尾试验(TST)中产生急性抗抑郁样效应。本研究旨在探讨信号通路在 FA 急性和口服给药的抗抑郁样作用中的可能参与,在 TST 中的作用。在 TST 中,预先用 H-89(1μg/部位,脑室内注射,PKA 抑制剂)、KN-62(1μg/部位,脑室内注射,CaMKII 抑制剂)、GF109203X(5ng/部位,脑室内注射,PKC 抑制剂)、U0126(5μg/部位,脑室内注射,MAPK/ERK 抑制剂)或 LY294002(10nmol/部位,脑室内注射,PI3K 抑制剂)预处理小鼠,可阻止口服给予 FA(0.01mg/kg,p.o.)的抗不动效应。这些结果表明,FA 通过激活与神经可塑性、神经发生和细胞存活相关的信号通路,在 TST 中发挥抗抑郁样作用。

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