Inhibition of SIRT1 in the nucleus accumbens attenuates heroin addiction-related behavior by decreasing D1 neuronal autophagy.

IF 1.6 4区 医学 Q4 NEUROSCIENCES Neuroreport Pub Date : 2024-05-08 Epub Date: 2024-03-14 DOI:10.1097/WNR.0000000000002033
Yanyan Huang, Meijun Liu, Zhiyao Zheng, Ruiping Lu, Chunlu Li, Min Su, Yixin Li, Baijuan Xia
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Abstract

This study aimed to investigate the effects of SIRT1 modulation on heroin addiction-like behavior and its possible biological mechanisms. Wild-type C57BL/6J and Sirt1loxp/loxp D1-Cre mice were used in this experiment, and Sirt1 loxp/loxp D1-Cre(-) mice were used as a control for conditional knockout mice. Mice were divided into saline control and heroin-dependent groups. Behavioral methods were used to record the withdrawal response, conditioned place preference (CPP) changes, and open field test results. Transmission electron microscopy (TEM) was used to observe the structure of autophagosomes in nucleus accumbens (NAc) neurons. The expression of SIRT1 and autophagy-related proteins and genes, such as LC3Ⅱ, ATG5 , and ATG7 , was detected in the NAc of each mouse group via western blot, real-time quantitative PCR (qPCR) analyzes, and immunofluorescence. The results of this experiment showed that compared with the saline group, mice in the wild-type heroin-dependent group showed marked withdrawal symptoms, with more autophagosomes observed in NAc via TEM. Compared with wild-type and Sirt1loxp/loxp D1-Cre(-) heroin-dependent groups, CPP formation was found to be reduced in the conditional knockout mouse group, with a significant decrease in spontaneous activity. Western blot, qPCR, and immunofluorescence results indicated that the expression of LC3Ⅱ, ATG-5, and ATG-7 was significantly reduced in the NAc of the Sirt1loxp/loxp D1-Cre(+) group. It was still, however, higher than that in the saline control group. These results suggest that inhibition of Sirt1 expression may prevent heroin-induced addiction-related behaviors via reducing D1 neuronal autophagy.

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通过减少 D1 神经元的自噬,抑制伏隔核中的 SIRT1 可减轻与海洛因成瘾相关的行为。
本研究旨在探讨调节SIRT1对海洛因成瘾样行为的影响及其可能的生物学机制。本实验使用野生型 C57BL/6J 和 Sirt1loxp/loxpD1-Cre 小鼠,Sirt1loxp/loxpD1-Cre(-) 小鼠作为条件性基因敲除小鼠的对照。小鼠被分为生理盐水对照组和海洛因依赖组。采用行为学方法记录戒断反应、条件性场所偏好(CPP)变化和开阔地测试结果。透射电子显微镜(TEM)用于观察神经核(NAc)中自噬体的结构。通过Western印迹、实时定量PCR(qPCR)分析和免疫荧光检测了各组小鼠NAc中SIRT1和自噬相关蛋白和基因(如LC3Ⅱ、ATG5和ATG7)的表达。实验结果表明,与生理盐水组相比,野生型海洛因依赖组小鼠表现出明显的戒断症状,通过TEM在NAc中观察到更多的自噬体。与野生型和Sirt1loxp/loxpD1-Cre(-)海洛因依赖组相比,条件性基因敲除小鼠组的CPP形成减少,自发活动显著降低。Western印迹、qPCR和免疫荧光结果表明,在Sirt1loxp/loxpD1-Cre(+)组的NAc中,LC3Ⅱ、ATG-5和ATG-7的表达明显减少。但仍高于生理盐水对照组。这些结果表明,抑制Sirt1的表达可通过减少D1神经元自噬防止海洛因诱发的成瘾相关行为。
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
Neuroreport
Neuroreport 医学-神经科学
CiteScore
3.20
自引率
0.00%
发文量
150
审稿时长
1 months
期刊介绍: NeuroReport is a channel for rapid communication of new findings in neuroscience. It is a forum for the publication of short but complete reports of important studies that require very fast publication. Papers are accepted on the basis of the novelty of their finding, on their significance for neuroscience and on a clear need for rapid publication. Preliminary communications are not suitable for the Journal. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool. The core interest of the Journal is on studies that cast light on how the brain (and the whole of the nervous system) works. We aim to give authors a decision on their submission within 2-5 weeks, and all accepted articles appear in the next issue to press.
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