Identification of a developmentally-regulated and psychostimulant-inducible novel rat gene mrt3 in the neocortex
Identification of a developmentally-regulated and psychostimulant-inducible novel rat gene mrt3 in the neocortex
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新皮质中发育调节和精神兴奋剂诱导的新型大鼠基因 mrt3 的鉴定
DOI：
10.1016/j.euroneuro.2014.07.010
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发表时间：
2014
影响因子：
5.6
通讯作者：
T. Nishikawa
中科院分区：
文献类型：
--
作者：
N. Yamamoto;S. Muraoka;Y. Kajii;A. Umino;T. Nishikawa
包括安非他明和可卡因在内的兴奋剂的拟精神病作用在人类和实验动物的出生后发育过程中会发生变化。为了深入了解兴奋剂诱导的精神病发病的分子基础，我们已经探索了基因转录，差异反应甲基苯丙胺（MAP）在发育中的大鼠大脑使用差异克隆技术，RNA任意引物PCR。我们确定了从大鼠新皮层的一种新的和发育调节MAP诱导基因rt 3（MAP响应转录3），转录到一个假定的非编码RNA的3.8 kb，位于反向链的F-box/LRR重复蛋白17-样基因映射到大鼠染色体Xq 12。Themrt 3 mRNA主要在脑和肺中表达。急性MAP注射上调themrt 3表达在出生后50天，但不是第8，15和23天，在D1受体拮抗剂敏感的方式。这种上调被另一种兴奋剂可卡因模仿，而戊巴比妥和D1拮抗剂未能改变他们的rt 3表达。此外，MAP重复处理5天可抑制MAP或可卡因激发剂量增加新皮质mrt 3表达的能力，而不影响停药第14天的basalmrt 3 mRNA水平。这些后期发展，可卡因交叉反应，D1拮抗剂敏感和长期的条例mrt 3 MAP是类似的兴奋剂诱导的行为敏化，模型的发病和复发的兴奋剂诱导的精神病和精神分裂症，因此可能与病理生理模型。
The psychotomimetic effects of stimulant drugs including amphetamines and cocaine are known to change during the postnatal development in humans and experimental animals. To obtain an insight into the molecular basis of the onset of stimulant-induced psychosis, we have explored the gene transcripts that differentially respond to methamphetamine (MAP) in the developing rat brains using a differential cloning technique, the RNA arbitrarily-primed PCR. We identified from the rat neocortex a novel and developmentally regulated MAP-inducible genemrt3(MAP responsive transcript 3) that is transcribed to a presumable non-coding RNA of 3.8 kb and is located on the reverse strand of the F-box/LRR-repeat protein 17-like gene mapped on the rat chromosome Xq12. Themrt3mRNAs are predominantly expressed in the brain and lung. Acute MAP injection upregulated themrt3expression in the neocortex at postnatal day 50, but not days 8, 15 and 23, in a D1 receptor antagonist-sensitive manner. This upregulation was mimicked by another stimulant, cocaine, whereas pentobarbital and D1 antagonist failed to alter themrt3expression. Moreover, repeated treatment with MAP for 5 days inhibited the ability of the challenge dose of MAP or cocaine to increase the neocorticalmrt3expression without affecting the basalmrt3mRNA levels on day 14 of withdrawal. These late-developing, cocaine-cross reactive, D1 antagonist-sensitive and long-term regulations ofmrt3by MAP are similar to those of stimulant-induced behavioral sensitization, a model of the onset and relapse of stimulant-induced psychosis and schizophrenia, and therefore may be associated with the pathophysiology of the model.
重复施用不同剂量的可卡因和 WIN 35,065-2 对小鼠运动行为的影响。
影响因子：
5
作者：
Reith,ME
通讯作者：
Reith,ME