Knockdown and overexpression of basolateral amygdala SIRT1 via AAV bidirectionally alter morphine-induced conditioned place preference extinction in mice.

IF 4.2 3区医学 Q2 NEUROSCIENCES

Frontiers in Cellular Neuroscience Pub Date : 2025-06-20 eCollection Date: 2025-01-01 DOI:10.3389/fncel.2025.1604914

Guo Hao, Yao Mingchen, Zheng Yalin, Qu Yaqi, Yang Tingwu, Xing Xinru, Li Kaixuan, Dong Yani, Liu Dongsen

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Abstract

Introduction: This study investigates the role of SIRT1 in basolateral amygdala (BLA) glutamatergic neurons in morphine-induced conditioned place preference (CPP).

Methods: Via SIRT1 knockdown/overexpression in bilateral BLA of morphine-induced CPP mice. Outcomes measured by behavioral tests, WB, and transmission electron microscopy.

Results: We found that SIRT1 knockdown prolonged CPP extinction and enhanced reinstatement, whereas overexpression accelerated extinction and attenuated relapse. Behavioral tests revealed that SIRT1 knockdown rescued morphine-induced memory impairment and anxiety-like behaviors, while overexpression exacerbated these effects. Ultrastructural and molecular analyses demonstrated SIRT1 modulation of synaptic plasticity-related proteins (BDNF, PSD95) and synaptic ultrastructure in BLA.

Discussion: Our findings reveal that SIRT1 bidirectionally regulates opioid-associated memory persistence through synaptic remodeling, highlighting its potential as an epigenetic target for addiction treatment. While SIRT1 is implicated in neuroplasticity, its specific role in modulating opioid-associated memory circuits within the BLA remains undefined, representing a critical gap in understanding addiction neuropathology.

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通过AAV敲低和过表达杏仁核基底外侧SIRT1可双向改变吗啡诱导的小鼠条件性位置偏好消退。

本研究探讨了SIRT1在吗啡诱导的条件位置偏好（CPP）中基底外侧杏仁核（BLA）谷氨酸能神经元中的作用。方法：通过SIRT1敲低/过表达吗啡诱导CPP小鼠双侧BLA。结果通过行为测试、WB和透射电子显微镜测量。结果：我们发现SIRT1敲低延长了CPP的消失和增强了恢复，而过表达加速了CPP的消失和减轻了复发。行为测试显示，SIRT1敲低可挽救吗啡诱导的记忆障碍和焦虑样行为，而过表达则加剧了这些影响。超微结构和分子分析表明SIRT1调节突触可塑性相关蛋白（BDNF, PSD95）和BLA的突触超微结构。讨论：我们的研究结果表明，SIRT1通过突触重塑双向调节阿片类药物相关的记忆持久性，突出了其作为成瘾治疗的表观遗传靶点的潜力。虽然SIRT1与神经可塑性有关，但其在调节BLA内阿片相关记忆回路中的具体作用仍未明确，这代表了理解成瘾神经病理学的关键空白。

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

Frontiers in Cellular Neuroscience NEUROSCIENCES-

CiteScore

7.90

自引率

3.80%

发文量

627

审稿时长

6-12 weeks

期刊介绍： Frontiers in Cellular Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the cellular mechanisms underlying cell function in the nervous system across all species. Specialty Chief Editors Egidio D‘Angelo at the University of Pavia and Christian Hansel at the University of Chicago are supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.