Selenoprotein P Modulates Methamphetamine Enhancement of Vesicular Dopamine Release in Mouse Nucleus Accumbens Via Dopamine D2 Receptors.
Selenoprotein P Modulates Methamphetamine Enhancement of Vesicular Dopamine Release in Mouse Nucleus Accumbens Via Dopamine D2 Receptors.
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DOI：
10.3389/fnins.2021.631825
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发表时间：
2021
影响因子：
4.3
通讯作者：
Bellinger FP
中科院分区：
文献类型：
--
作者：
Torres DJ;Yorgason JT;Mitchell CC;Hagiwara A;Andres MA;Kurokawa S;Steffensen SC;Bellinger FP
多巴胺（DA）的传递在奖赏和愉悦刺激的加工过程中起着关键作用。突触多巴胺释放的增加是滥用药物的生理效应的重要组成部分。必需微量元素硒减轻甲基苯丙胺诱导的神经毒性。硒还可以改变DA的产生和周转。然而，研究还没有直接解决硒在DA神经传递中的作用。硒蛋白P（SELENOP 1）需要硒来合成，并将硒转运到大脑，此外还执行其他功能。我们研究了SELENOP 1是否直接影响（1）DA信号传导和（2）对甲基苯丙胺的多巴胺能反应。我们使用快速扫描循环伏安法来研究DA传输和对C57/BL 6 J SELENOP 1 KO小鼠NAc切片中甲基苯丙胺的反应。来自SELENOP 1 KO小鼠切片的记录显示，诱发的DA释放水平降低，DA摄取速率减慢。甲基苯丙胺导致SELENOP 1 KO小鼠的囊泡DA释放急剧增加，而野生型对照中未观察到这一点。通过硒非依赖性机制（涉及硒-载脂蛋白E受体2（ApoER 2）相互作用以促进多巴胺D2受体（D2 R）功能），应用硒-磷酸腺苷1可减弱这种升高的反应。在野生型小鼠中，通过阻断D2 R激活，发现甲基苯丙胺引起的囊泡DA释放增加，表明受体抑制甲基苯丙胺诱导的囊泡增加。我们的数据提供的证据表明，在多巴胺能反应的甲基苯丙胺的直接生理作用，并建议在DA传输的蛋白质的信号作用。
Dopamine (DA) transmission plays a critical role in processing rewarding and pleasurable stimuli. Increased synaptic DA release in the nucleus accumbens (NAc) is a central component of the physiological effects of drugs of abuse. The essential trace element selenium mitigates methamphetamine-induced neurotoxicity. Selenium can also alter DA production and turnover. However, studies have not directly addressed the role of selenium in DA neurotransmission. Selenoprotein P (SELENOP1) requires selenium for synthesis and transports selenium to the brain, in addition to performing other functions. We investigated whether SELENOP1 directly impacts (1) DA signaling and (2) the dopaminergic response to methamphetamine. We used fast-scan cyclic voltammetry to investigate DA transmission and the response to methamphetamine in NAc slices from C57/BL6J SELENOP1 KO mice. Recordings from SELENOP1 KO mouse slices revealed reduced levels of evoked DA release and slower DA uptake rates. Methamphetamine caused a dramatic increase in vesicular DA release in SELENOP1 KO mice not observed in wild-type controls. This elevated response was attenuated by SELENOP1 application through a selenium-independent mechanism involving SELENOP1-apolipoprotein E receptor 2 (ApoER2) interaction to promote dopamine D2 receptor (D2R) function. In wild-type mice, increased vesicular DA release in response to methamphetamine was revealed by blocking D2R activation, indicating that the receptor suppresses the methamphetamine-induced vesicular increase. Our data provide evidence of a direct physiological role for SELENOP1 in the dopaminergic response to methamphetamine and suggest a signaling role for the protein in DA transmission.
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影响因子：
4.8
作者：
Burk, Raymond F.;Hill, Kristina E.;Zhang, Wanqi
通讯作者：
Zhang, Wanqi
影响因子：
3.4
作者：
Covey, Dan P.;Bunner, Kendra D.;Garris, Paul A.
通讯作者：
Garris, Paul A.
DOI：
10.1016/j.jtemb.2007.11.003
发表时间：
2008-01-01
影响因子：
3.5
作者：
Hollenbach, Birgit;Morgenthaler, Nils G.;Schomburg, Lutz
通讯作者：
Schomburg, Lutz
影响因子：
16.6
作者：
Condon, Mark D.;Platt, Nicola J.;Cragg, Stephanie J.
通讯作者：
Cragg, Stephanie J.
影响因子：
4.2
作者：
Castano, A;Ayala, A;Machado, A
通讯作者：
Machado, A