关键词: cycloheximide neurotransmitters oxidative damage passive avoidance task puerarin

Mesh : Rats Animals Cycloheximide / adverse effects Memory Consolidation Antioxidants Memory Disorders / chemically induced drug therapy Oxidative Stress Neurotransmitter Agents / adverse effects Isoflavones

来  源:   DOI:10.31083/j.jin2301017

Abstract:
BACKGROUND: Cycloheximide (CXM), an antifungal antibiotic, causes impaired memory consolidation as a side effect partially by disturbing the activities of the central catecholaminergic and cholinergic system. Some reports indicated that puerarin prevented memory impairment in various models in rodents. However, the protective effects of puerarin on the side effects of cycloheximide for memory consolidation impairment have not yet been investigated.
METHODS: The protective effects of puerarin on CXM-induced memory-consolidation impairment, and memory impairment produced by central administration of AF64A neurotoxin, were investigated using a passive avoidance task in rats. A combination of transmitter receptor agonists and antagonists was used to explore the effects of puerarin on nervous system function. The activity of antioxidant defense systems and neurotransmitter systems in the prefrontal cortex and hippocampus were assayed.
RESULTS: Systemic (25 and 50 mg/kg, i.p.) or central (5 and 10 µg/brain, i.c.v.) administration of puerarin attenuated CXM-induced memory-consolidation impairment produced by 1.5 mg/kg CXM (s.c.) in rats. The improvements produced by 50 mg/kg puerarin were blocked by cholinergic antagonists, a 5-HT2 receptor agonist, and an adrenergic receptor antagonist. Puerarin (only at 50 mg/kg, i.p.) reversed the CXM-induced alterations of the levels of norepinephrine in the prefrontal cortex and the levels of monoamines in the hippocampus. Puerarin also increased antioxidant-defense-system activities in the prefrontal cortex and hippocampus, which had been decreased by CXM.
CONCLUSIONS: We suggested that the attenuating effects of puerarin on CXM-induced memory-consolidation impairment may be due to decrease oxidative damage and the normalition of the neurotransmitter function in the prefrontal cortex and hippocampus.
摘要:
背景:环己基酰亚胺(CXM),一种抗真菌抗生素,部分由于干扰中枢儿茶酚胺能和胆碱能系统的活动而导致记忆巩固受损。一些报告表明,葛根素可以预防啮齿动物各种模型的记忆障碍。然而,葛根素对环己酰亚胺对记忆巩固障碍的副作用的保护作用尚未研究。
方法:葛根素对CXM诱导的记忆巩固障碍的保护作用,和由中心施用AF64A神经毒素产生的记忆障碍,在大鼠中使用被动回避任务进行了研究。用递质受体激动剂和拮抗剂联合研究葛根素对神经系统功能的影响。测定了前额叶皮质和海马中抗氧化防御系统和神经递质系统的活性。
结果:全身(25和50mg/kg,i.p.)或中枢(5和10µg/脑,i.c.v.)葛根素的施用减轻了1.5mg/kgCXM(s.c.)在大鼠中产生的CXM诱导的记忆巩固障碍。50mg/kg葛根素产生的改善被胆碱能拮抗剂阻断,一种5-HT2受体激动剂,和肾上腺素能受体拮抗剂.葛根素(仅在50mg/kg,i.p.)逆转了CXM诱导的前额叶皮质去甲肾上腺素水平和海马单胺水平的变化。葛根素还增加了前额叶皮层和海马的抗氧化防御系统活性,被CXM减少了。
结论:我们认为葛根素减轻CXM诱导的记忆巩固障碍的作用可能是由于减少了氧化损伤和前额叶皮质和海马神经递质功能的正常化。
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