Genetic deletion of Rgs12 in mice affects serotonin transporter expression and function in vivo and ex vivo.
Genetic deletion of Rgs12 in mice affects serotonin transporter expression and function in vivo and ex vivo.
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DOI：
10.1177/0269881120944160
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Setola V
中科院分区：
文献类型：
--
作者：
White AN;Gross JD;Kaski SW;Trexler KR;Wix KA;Wetsel WC;Kinsey SG;Siderovski DP;Setola V
G蛋白信号转导调节因子(RGS)蛋白抑制G蛋白偶联受体(GPCR)信号，包括神经递质释放所产生的信号。我们已经证明，RGS12缺失降低了C57BL/6J小鼠对多巴胺转运体(DAT)靶向精神刺激剂的运动反应。这种减少是由于RGS12基因缺失小鼠的DAT表达和功能的脑区特异性上调所致。这种对DAT的影响促使我们调查C57BL/6J小鼠的5-羟色胺转运体(SERT)是否在RGS12丢失时表现出类似的变化。RGS12缺失是否影响1)SERT优先靶向精神刺激剂3，4-亚甲基二氧基甲基苯丙胺(MDMA)的超运动，2)SERT在相关脑区的表达和功能，和/或3)血清素调节的行为？对开阔场地和自发的家庭笼养活动进行量化。采用适当的生化分析方法检测脑区组织匀浆中5-羟色胺、5-羟IAA和SERT的水平，以及脑区组织标本中SERT的表达和功能。通过强迫游泳和尾部悬吊范例、高架正式和高架零迷宫测试以及社会互动分析来评估血清神经调节行为。RGS12基因缺失的小鼠对10 mg/kg的MDMA没有表现出多动行为。与RGS12缺失相关的SERT表达和功能存在脑区特异性改变。药物天真的RGS12基因缺失的小鼠在焦虑样行为和抗抑郁样行为方面都显示出增加。RGS12是5-羟色胺能神经传递和5-羟色胺调节行为的关键调节剂；RGS12基因缺失的小鼠缺乏对低剂量MDMA的过度运动与稳态SERT表达和5-羟色胺摄取的改变有关。
Regulator of G protein Signaling (RGS) proteins inhibit G protein-coupled receptor (GPCR) signaling, including the signals that arise from neurotransmitter release. We have shown that RGS12 loss diminishes locomotor responses of C57BL/6J mice to dopamine transporter (DAT)-targeting psychostimulants. This diminution resulted from a brain region-specific upregulation of DAT expression and function in RGS12-null mice. This effect on DAT prompted us to investigate whether the serotonin transporter (SERT) exhibits similar alterations upon RGS12 loss in C57BL/6J mice. Does RGS12 loss affect 1) hyperlocomotion to the preferentially SERT-targeting psychostimulant 3,4-methylenedioxymethamphetamine (MDMA), 2) SERT expression and function in relevant brain regions, and/or 3) serotonergically modulated behaviors? Open-field and spontaneous home-cage locomotor activities were quantified. 5-HT, 5-HIAA, and SERT levels in brain-region homogenates, as well as SERT expression and function in brain-region tissue preparations, were measured using appropriate biochemical assays. Serotonergically modulated behaviors were assessed using forced swim and tail suspension paradigms, elevated plus and elevated zero maze tests, and social interaction assays. RGS12-null mice displayed no hyperlocomotion to 10 mg/kg MDMA. There were brain region-specific alterations in SERT expression and function associated with RGS12 loss. Drug-naïve RGS12-null mice displayed increases in both anxiety-like and anti-depressive-like behaviors. RGS12 is a critical modulator of serotonergic neurotransmission and serotonergically modulated behavior in mice; lack of hyperlocomotion to low dose MDMA in RGS12-null mice is related to an alteration of steady-state SERT expression and 5-HT uptake.
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DOI：
10.1186/1471-2210-6-6
发表时间：
2006-03-03
期刊：
BMC pharmacology
影响因子：
--
作者：
Han DD;Gu HH
通讯作者：
Gu HH
DOI：
10.1177/0269881117725915
发表时间：
2017-09
期刊：
Journal of psychopharmacology (Oxford, England)
影响因子：
--
作者：
Carhart-Harris RL;Nutt DJ
通讯作者：
Nutt DJ
影响因子：
4.7
作者：
Hilber, B;Scholze, P;Sitte, HH
通讯作者：
Sitte, HH
影响因子：
10.6
作者：
Holmes, A;Murphy, DL;Crawley, JN
通讯作者：
Crawley, JN
影响因子：
7.6
作者：
Holmes, A;Yang, RJ;Crawley, JN
通讯作者：
Crawley, JN