miR-483-5p offsets functional and behavioural effects of stress in male mice through synapse-targeted repression of Pgap2 in the basolateral amygdala.
miR-483-5p offsets functional and behavioural effects of stress in male mice through synapse-targeted repression of Pgap2 in the basolateral amygdala.
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DOI：
10.1038/s41467-023-37688-2
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发表时间：
2023-04-25
影响因子：
16.6
通讯作者：
Pawlak, Robert
中科院分区：
文献类型：
--
作者：
Mucha, Mariusz;Skrzypiec, Anna E.;Kolenchery, Jaison B.;Brambilla, Valentina;Patel, Satyam;Labrador-Ramos, Alberto;Kudla, Lucja;Murrall, Kathryn;Skene, Nathan;Dymicka-Piekarska, Violetta;Klejman, Agata;Przewlocki, Ryszard;Mosienko, Valentina;Pawlak, Robert
严重的心理创伤会引发杏仁核神经元的遗传、生物化学和形态变化，从而导致压力引起的行为异常，如高度焦虑。miRNA是小的非编码RNA片段，其通过多个靶基因的同时转录/翻译抑制来协调复杂的神经元反应。在这里，我们表明雄性小鼠杏仁核中的miR-483- 5 p平衡了压力的结构，功能和行为后果，以促进焦虑样行为的减少。应激时，miR-483- 5 p在杏仁核神经元的突触区室中上调，并直接抑制三种应激相关基因：Pgap 2、Gpx 3和Macf 1。miR-483- 5 p的上调导致树突状动脉远端部分的选择性收缩，并将未成熟的丝状伪足转化为成熟的蘑菇样树突棘。与其在减少应激反应中的作用一致，基底外侧杏仁核中miR-483- 5 p的上调产生焦虑样行为的减少。应激诱导的miR-483- 5 p的神经形态学和行为学效应可以通过shRNA介导的Pgap 2抑制来重现，并通过同时过表达miR-483- 5 p抗性Pgap 2来预防。我们的研究结果表明，miR-483- 5 p足以减少焦虑样行为，并指出miR-483- 5 p介导的Pgap 2抑制是抵消心理压力的功能和行为后果的关键细胞事件。miRNAs在调节脑应激反应中的作用仍然相对未被探索。在这里，作者表明miR-483- 5 p介导的雄性小鼠杏仁核中Pgap 2的抑制抵消了应激的功能和行为后果。
Severe psychological trauma triggers genetic, biochemical and morphological changes in amygdala neurons, which underpin the development of stress-induced behavioural abnormalities, such as high levels of anxiety. miRNAs are small, non-coding RNA fragments that orchestrate complex neuronal responses by simultaneous transcriptional/translational repression of multiple target genes. Here we show that miR-483-5p in the amygdala of male mice counterbalances the structural, functional and behavioural consequences of stress to promote a reduction in anxiety-like behaviour. Upon stress, miR-483-5p is upregulated in the synaptic compartment of amygdala neurons and directly represses three stress-associated genes: Pgap2, Gpx3 and Macf1. Upregulation of miR-483-5p leads to selective contraction of distal parts of the dendritic arbour and conversion of immature filopodia into mature, mushroom-like dendritic spines. Consistent with its role in reducing the stress response, upregulation of miR-483-5p in the basolateral amygdala produces a reduction in anxiety-like behaviour. Stress-induced neuromorphological and behavioural effects of miR-483-5p can be recapitulated by shRNA mediated suppression of Pgap2 and prevented by simultaneous overexpression of miR-483-5p-resistant Pgap2. Our results demonstrate that miR-483-5p is sufficient to confer a reduction in anxiety-like behaviour and point to miR-483-5p-mediated repression of Pgap2 as a critical cellular event offsetting the functional and behavioural consequences of psychological stress. The role of miRNAs in regulating brain stress response remains relatively unexplored. Here the authors show that miR-483-5p-mediated repression of Pgap2 in amygdala of male mice offsets the functional and behavioural consequences of stress.
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影响因子：
16.2
作者：
Dias, Brian George;Goodman, Jared Vega;Ahluwalia, Ranbir;Easton, Audrey Elizabeth;Andero, Rauel;Ressler, Kerry James
通讯作者：
Ressler, Kerry James
影响因子：
16.2
作者：
Bosch M;Castro J;Saneyoshi T;Matsuno H;Sur M;Hayashi Y
通讯作者：
Hayashi Y
影响因子：
16.2
作者：
Edbauer, Dieter;Neilson, Joel R.;Foster, Kelly A.;Wang, Chi-Fong;Seeburg, Daniel P.;Batterton, Matthew N.;Tada, Tomoko;Dolan, Bridget M.;Sharp, Phillip A.;Sheng, Morgan
通讯作者：
Sheng, Morgan
从杏仁核中的电路到行为。
影响因子：
64.8
作者：
Janak PH;Tye KM
通讯作者：
Tye KM
影响因子：
25
作者：
Pawlak, R;Magarinos, AM;Strickland, S
通讯作者：
Strickland, S