9-Cis retinoic acid protects against methamphetamine-induced neurotoxicity in nigrostriatal dopamine neurons.
9-Cis retinoic acid protects against methamphetamine-induced neurotoxicity in nigrostriatal dopamine neurons.
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DOI：
10.1007/s12640-013-9413-4
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发表时间：
2014-04
影响因子：
3.7
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Reiner DJ;Yu SJ;Shen H;He Y;Bae E;Wang Y
甲基苯丙胺（MA）是一种滥用药物，也是一种多巴胺能神经毒素。 9-顺式视黄酸 (9cRA) 是维生素 A 的一种生物活性衍生物，在体外对 H2O2 和缺氧缺糖引起的损伤以及缺血性脑梗死和 TUNEL 标记具有保护作用。本研究的目的是检查 9cRA 是否对黑质纹状体多巴胺能神经元中的 MA 毒性具有保护作用。用MA处理从大鼠胚胎腹侧中脑组织制备的原代多巴胺能神经元。高剂量的 MA 降低了酪氨酸羟化酶 (TH) 的免疫反应性，同时增加了 TUNEL 标记。 9cRA 显着降低了这些毒性。 9cRA 还抑制 Nur77 从细胞核到细胞质的输出，这是一种激活细胞凋亡的反应。接下来在成年大鼠中检查了 9cRA 和 MA 体内的相互作用。 9cRA 经脑室内给药；一天后给予 MA（5 mg/kg，4x）。手术后两天测量了 48 小时内的运动行为。高剂量的 MA 显着降低了纹状体的运动活性和 TH 免疫反应性。 9cRA 的施用对抗了这些变化。先前的研究表明，9cRA 可以诱导骨形态发生蛋白 7 (BMP7) 表达，并且 BMP7 的施用可减轻 MA 毒性。我们证明 MA 处理显着降低黑质中 BMP7 mRNA 的表达。 Noggin（一种 BMP 拮抗剂）拮抗 9cRA 诱导的行为恢复和 9cRA 诱导的纹状体 TH 水平正常化。我们的数据表明，9cRA 通过上调 BMP 对多巴胺能神经元中 MA 介导的神经变性具有保护作用。
Methamphetamine (MA) is a drug of abuse as well as a dopaminergic neurotoxin. 9-cis retinoic acid (9cRA), a biologically active derivative of vitamin A, has protective effects against damage caused by H2O2 and oxygen-glucose deprivation in vitro as well as infarction and TUNEL labeling in ischemic brain. The purpose of this study was to examine if there was a protective role for 9cRA against MA toxicity in nigrostriatal dopaminergic neurons. Primary dopaminergic neurons, prepared from rat embryonic ventral mesencephalic tissue, were treated with MA. High doses of MA decreased tyrosine hydroxylase (TH) immunoreactivity while increasing TUNEL labeling. These toxicities were significantly reduced by 9cRA. 9cRA also inhibited the export of Nur77 from nucleus to cytosol, a response that activates apoptosis. The interaction of 9cRA and MA in vivo was next examined in adult rats. 9cRA was delivered intracerebroventricularly; MA was given (5 mg/kg, 4x) one day later. Locomotor behavior was measured two days after surgery for a period of 48 hours. High doses of MA significantly reduced locomotor activity and TH immunoreactivity in striatum. Administration of 9cRA antagonized these changes. Previous studies have shown that 9cRA can induce bone morphogenetic protein-7 (BMP7) expression and that administration of BMP7 attenuates MA toxicity. We demonstrated that MA treatment significantly reduced BMP7 mRNA expression in nigra. Noggin (a BMP antagonist) antagonized 9cRA-induced behavioral recovery and 9cRA-induced normalization of striatal TH levels. Our data suggest that 9cRA has a protective effect against MA -mediated neurodegeneration in dopaminergic neurons via upregulation of BMP.
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影响因子：
8.9
作者：
Bazan NG;Molina MF;Gordon WC
通讯作者：
Gordon WC
影响因子：
3.4
作者：
Cheung, Yuen-Ting;Lau, Way Kwok-Wai;Chang, Raymond Chuen-Chung
通讯作者：
Chang, Raymond Chuen-Chung
影响因子：
2.5
作者：
Shen, Hui;Luo, Yu;Wang, Yun
通讯作者：
Wang, Yun
DOI：
10.1016/s0169-328x(01)00184-x
发表时间：
2001-09-10
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Deng, XL;Wang, Y;Cadet, JL
通讯作者：
Cadet, JL
影响因子：
4.2
作者：
BONIECE, IR;WAGNER, JA
通讯作者：
WAGNER, JA