多巴胺D2受体调节mPFC-BLA回路与慢性睡眠剥夺引起的小鼠记忆障碍有关。

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Theranostics Pub Date : 2025-08-16 eCollection Date: 2025-01-01 DOI:10.7150/thno.114797
Jiaxuan Yang, Jiahui Sun, Zili Liu, Xia Tang, Yunyun Hu, Weida Shen, Yicheng Xie, Yue Jin, Haifeng Li, Xuekun Li, Yanjun Jiang, Matthew Tak Vai Chan, William Ka Kei Wu, Zhigang Liu, Xiaodong Liu, Yaoqin Hu, Jinpiao Zhu, Daqing Ma
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引用次数: 0

摘要

背景:慢性睡眠剥夺(CSD)影响神经网络的协调,导致认知障碍,但潜在的分子和神经回路机制尚不清楚。方法:小鼠接受为期两周的CSD治疗,随后采用y迷宫测试和脑电图伽马振荡分析评估空间记忆。利用转录组学和免疫荧光分析评估多巴胺D2受体(Drd2)在内侧前额叶皮层(mPFC)中的表达。通过向mPFC局部输注Drd2激动剂或拮抗剂,研究了Drd2在csd诱导的记忆缺陷中的作用。采用神经回路示踪、纤维光度法和光化学发生方法来评估Drd2在CSD诱导的mpfc -基底外侧杏仁核(BLA)回路介导的记忆损伤中的门控作用。结果:CSD解除了多巴胺输入到mPFC的抑制作用,使小鼠的空间记忆受损。cdd后mPFC II/III层Drd2表达显著增加。将Drd2激动剂注入naïve小鼠的mPFC诱导记忆缺陷,而给予Drd2拮抗剂可逆转CSD引起的记忆损伤。Drd2被发现与Ca2+/钙调素依赖性蛋白激酶IIα (CaMKIIα+)神经元共定位于mPFC中投射到基底外侧杏仁核(BLA)的神经元。激活CaMKIIα+神经元通过增强mpfc - bla输出恢复CSD诱导的记忆障碍,逆转Drd2激动剂诱导的记忆缺陷。结论:我们的研究结果表明,过量的Drd2信号通过抑制mPFC-BLA神经传递导致CSD后认知功能障碍,提示多巴胺D2受体拮抗剂在缓解CSD诱导的认知功能下降方面可能具有治疗价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dopamine D2 receptor modulating mPFC-BLA circuit contributes to chronic sleep deprivation-induced memory impairment in mice.

Background: Chronic sleep deprivation (CSD) affects the orchestration of neural networks, leading to cognitive impairment, but the underlying molecular and neural circuitry mechanisms remain unknown. Methods: Mice underwent a two-week CSD regimen, followed by spatial memory assessment using the Y-maze test and EEG gamma oscillation analysis. Dopamine D2 receptor (Drd2) expression in the medial prefrontal cortex (mPFC) was evaluated using transcriptomic and immunofluorescent analysis. The role of Drd2 in CSD-induced memory deficits was examined through local infusion of Drd2 agonists or antagonists into the mPFC. Neural circuit tracing, fiber photometry, and opto-chemogenetic approaches were used to assess Drd2 in the gating of the mPFC-basolateral amygdala (BLA) circuit-mediated memory impairment induced by CSD. Results: CSD disinhibited dopaminergic input to the mPFC and impaired spatial memory in mice. A significant increase in Drd2 expression was found in the layers II/III of the mPFC after CSD. Infusion of Drd2 agonist into the mPFC induced memory deficits in naïve mice, while administration of the Drd2 antagonist reversed memory impairment caused by CSD. Drd2 was found to co-localize with Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα+) neurons in the mPFC that project to the basolateral amygdala (BLA). Activation of CaMKIIα+ neurons restored memory impairment induced by CSD through enhancing mPFC-to-BLA output and reversed memory defects induced by the Drd2 agonist. Conclusion: Our findings demonstrated that excessive Drd2 signaling leads to cognitive impairment following CSD by suppressing mPFC-BLA neurotransmission, suggesting a possible therapeutic value of dopamine D2 receptor antagonists in relieving CSD-induced cognitive decline.

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来源期刊
Theranostics
Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
25.40
自引率
1.60%
发文量
433
审稿时长
1 months
期刊介绍: Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.
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