Effects of N-acetylcysteine after repeated exposure to ethanol in memory and neurotransmission in zebrafish

IF 2.6 3区医学 Q3 NEUROSCIENCES

Neurotoxicology and teratology Pub Date : 2025-06-12 DOI:10.1016/j.ntt.2025.107508

Daiana Alves Spilere, Guilherme Lodetti, Ana Carolina Salvador de Farias, Amanda Gomes Teixeira, Eduardo Ronconi Dondossola, Eduardo Pacheco Rico

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引用次数: 0

Abstract

Introduction

In the brain, alcohol metabolites alter the functioning of several neurotransmission systems, such as glutamatergic and cholinergic, in addition to impairing memory and learning. Medications for Alcohol Use Disorders (AUD) cause adverse effects and contraindications. N-acetylcysteine (NAC) has been shown to protect memory and restore acetylcholinesterase (AChE) levels. Additionally, it functions as an antioxidant that works alongside glutathione, which is associated with the glutamatergic synapse. In this context, the current research aimed to examine the neuroprotective effects of NAC in animals that underwent repeated ethanol exposure (REE), along with the impacts on memory and the cholinergic and glutamatergic signaling pathways in zebrafish.

Methods

The animals were exposed to 1 % ethanol for 8 days for 20 min daily. They received treatment with NAC after the eighth exposure to ethanol for 10 or 60 min. Euthanasia occurred 24 h after the last exposure. Inhibitory avoidance and object recognition tests were performed. Also, the choline acetyltransferase (ChAT) enzyme activities, AChE activity, and glutamate uptake were evaluated.

Results

The results show a significant AChE activity increase in the REE group and a decrease in those exposed to alcohol and treated with NAC for 10 min. No significant differences were found regarding ChAT activity. REE significantly reduced glutamate uptake. All groups except the ethanol group acquired aversive memory in inhibitory avoidance tests. Only the NAC-treated group demonstrated longer new object exploration in the recognition test. The study indicates that REE affects AChE, glutamate uptake, and aversive memory and that a single NAC treatment can mitigate these effects. These findings enhance the understanding of REE mechanisms and NAC's protective properties against ethanol-induced damage in zebrafish.

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反复暴露于乙醇后n -乙酰半胱氨酸对斑马鱼记忆和神经传递的影响。

简介：在大脑中，酒精代谢物除了损害记忆和学习能力外，还会改变几种神经传递系统的功能，如谷氨酸能和胆碱能。治疗酒精使用障碍（AUD）的药物会导致不良反应和禁忌症。n -乙酰半胱氨酸（NAC）已被证明具有保护记忆和恢复乙酰胆碱酯酶（AChE）水平的作用。此外，它作为一种抗氧化剂，与谷胱甘肽一起作用，谷胱甘肽与谷氨酸能突触有关。在此背景下，目前的研究旨在研究NAC对反复乙醇暴露（REE）的动物的神经保护作用，以及对斑马鱼记忆和胆碱能和谷氨酸能信号通路的影响。方法：1 %乙醇浸泡8 天，每天20 min。他们在第八次暴露于乙醇10或60 分钟后接受NAC治疗。安乐死发生在最后一次接触后24 小时。进行了抑制性回避和目标识别测试。测定了胆碱乙酰转移酶（ChAT）活性、乙酰胆碱酯交换酶（AChE）活性和谷氨酸摄取。结果：结果显示，REE组乙酰胆碱酯酶活性显著增加，暴露于酒精和NAC治疗10 min组乙酰胆碱酯酶活性降低。在ChAT活性方面没有发现显著差异。REE显著降低谷氨酸摄取。在抑制回避试验中，除乙醇组外，其余各组均获得了厌恶记忆。只有nac处理组在识别测试中表现出更长时间的新物体探索。研究表明REE影响乙酰胆碱酯酶、谷氨酸摄取和厌恶记忆，单一NAC治疗可以减轻这些影响。这些发现增强了对REE机制和NAC对斑马鱼乙醇损伤的保护作用的理解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurotoxicology and teratology 医学-毒理学

CiteScore

5.60

自引率

10.30%

发文量

审稿时长

58 days

期刊介绍： Neurotoxicology and Teratology provides a forum for publishing new information regarding the effects of chemical and physical agents on the developing, adult or aging nervous system. In this context, the fields of neurotoxicology and teratology include studies of agent-induced alterations of nervous system function, with a focus on behavioral outcomes and their underlying physiological and neurochemical mechanisms. The Journal publishes original, peer-reviewed Research Reports of experimental, clinical, and epidemiological studies that address the neurotoxicity and/or functional teratology of pesticides, solvents, heavy metals, nanomaterials, organometals, industrial compounds, mixtures, drugs of abuse, pharmaceuticals, animal and plant toxins, atmospheric reaction products, and physical agents such as radiation and noise. These reports include traditional mammalian neurotoxicology experiments, human studies, studies using non-mammalian animal models, and mechanistic studies in vivo or in vitro. Special Issues, Reviews, Commentaries, Meeting Reports, and Symposium Papers provide timely updates on areas that have reached a critical point of synthesis, on aspects of a scientific field undergoing rapid change, or on areas that present special methodological or interpretive problems. Theoretical Articles address concepts and potential mechanisms underlying actions of agents of interest in the nervous system. The Journal also publishes Brief Communications that concisely describe a new method, technique, apparatus, or experimental result.