Trace amine-associated receptor 1 regulation of methamphetamine-induced neurotoxicity.
Trace amine-associated receptor 1 regulation of methamphetamine-induced neurotoxicity.
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DOI：
10.1016/j.neuro.2017.09.006
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发表时间：
2017-12
期刊：
影响因子：
3.4
通讯作者：
Janowsky A
中科院分区：
文献类型：
--
作者：
Miner NB;Elmore JS;Baumann MH;Phillips TJ;Janowsky A
微量胺相关受体1(TAAR1)被甲基苯丙胺(MA)激活并调节多巴胺能(DA)功能。尽管DA调节失调是MA诱导的神经毒性导致行为和认知障碍的标志，但TAAR1的中介作用尚未确定。为探讨TAAR1基因敲除(KO)和野生型(WT)小鼠TAAR1对MA神经毒性的调节作用。注射MA(2.5、5或10 mg/kg)，间隔2小时。治疗当天记录体温数据。此外，在MA给药后2天或7天采集纹状体组织，分析DA、3，4-二羟基苯乙酸(DOPAC)、高香草酸(HVA)和酪氨酸羟基酶(TH)的水平以及胶质纤维酸性蛋白(GFAP)的表达。在Taar1-WT小鼠中，MA引起了急性体温下降，但在Taar1-KO小鼠中却没有。治疗两天后，与Taar1-WT小鼠相比，Taar1-KO小鼠的DA和TH水平较低，且MA呈剂量依赖性降低。在两个时间点，所有剂量的MA都显著增加了GFAP的表达，并且与接受MA2.5或5 mg/kg的Taar1-WT小鼠相比，Taar1-KO组的GFAP表达更强。7天后，DA水平以类似的模式下降：与接受MA2.5或5 mg/kg的Taar1-WT小鼠相比，Taar1-KO组的DA水平显著降低。无论是哪种基因型，MA均可使TH水平均匀降低。这些结果表明，TAAR1的激活增强了MA诱导的低温，TAAR1依赖于其体温调节作用而提供持续的神经保护。
Trace amine-associated receptor 1 (TAAR1) is activated by methamphetamine (MA) and modulates dopaminergic (DA) function. Although DA dysregulation is the hallmark of MA-induced neurotoxicity leading to behavioral and cognitive deficits, the intermediary role of TAAR1 has yet to be characterized. To investigate TAAR1 regulation of MA-induced neurotoxicity, Taar1 transgenic knock-out (KO) and wildtype (WT) mice were administered saline or a neurotoxic regimen of 4 i.p. injections, 2 hr apart, of MA (2.5, 5, or 10 mg/kg). Temperature data were recorded during the treatment day. Additionally, striatal tissue was collected 2 or 7 days following MA administration for analysis of DA, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and tyrosine hydroxylase (TH) levels, as well as glial fibrillary acidic protein (GFAP) expression. MA elicited an acute hypothermic drop in body temperature in Taar1-WT mice, but not in Taar1-KO mice. Two days following treatment, DA and TH levels were lower in Taar1-KO mice compared to Taar1-WT mice, regardless of treatment, and were dose-dependently decreased by MA. GFAP expression was significantly increased by all doses of MA at both time points and greater in Taar1-KO compared to Taar1-WT mice receiving MA 2.5 or 5 mg/kg. Seven days later, DA levels were decreased in a similar pattern: DA was significantly lower in Taar1-KO compared to Taar1-WT mice receiving MA 2.5 or 5 mg/kg. TH levels were uniformly decreased by MA, regardless of genotype. These results indicate that activation of TAAR1 potentiates MA-induced hypothermia and TAAR1 confers sustained neuroprotection dependent on its thermoregulatory effects.
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安非他明、3,4-亚甲二氧基甲基苯丙胺、麦角酸二乙酰胺和儿茶酚胺神经递质的代谢物是大鼠微量胺受体的激动剂
影响因子：
3.6
作者：
Bunzow, JR;Sonders, MS;Grandy, DK
通讯作者：
Grandy, DK
影响因子：
7.6
作者：
Ares-Santos, Sara;Granado, Noelia;Moratalla, Rosario
通讯作者：
Moratalla, Rosario
影响因子：
4.7
作者：
Cisneros IE;Ghorpade A
通讯作者：
Ghorpade A
DOI：
10.1073/pnas.0906522106
发表时间：
2009-11-24
影响因子：
11.1
作者：
Bradaia, Amyaouch;Trube, Gerhard;Bettler, Bernhard
通讯作者：
Bettler, Bernhard
DOI：
10.4161/23328940.2014.982049
发表时间：
2014-10
期刊：
Temperature (Austin, Tex.)
影响因子：
--
作者：
Bowyer JF;Hanig JP
通讯作者：
Hanig JP