Identification of developmentally regulated PCP-responsive non-coding RNA, prt6, in the rat thalamus.
Identification of developmentally regulated PCP-responsive non-coding RNA, prt6, in the rat thalamus.
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DOI：
10.1371/journal.pone.0097955
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Nishikawa T
中科院分区：
文献类型：
--
作者：
Takebayashi H;Yamamoto N;Umino A;Nishikawa T
nmda型谷氨酸受体拮抗剂如苯环利定（PCP）和氯胺酮引起的精神分裂症和类似精神病通常在青春期后发生。此外，在NMDA受体拮抗剂应用于啮齿动物后，在出生后约3周的关键时期观察到成人型行为障碍。这些观察结果表明，NMDA拮抗剂引起的精神分裂症症状和拟精神作用需要某些脑神经回路和分子网络的成熟，这些神经回路和分子网络在青春期和关键时期对NMDA受体拮抗剂的反应是不同的。从这个角度来看，我们已经从大鼠丘脑中发现了一种新的发育调节苯利定应答转录物，称为prt6，作为上述精神分裂症相关系统的候选分子。该转录本是一种非编码RNA，包括至少两种microrna miR132和miR212的序列，在大脑和睾丸中强烈表达，在脾脏、心脏、肝脏、肾脏、肺和骨骼肌中有微量或不可检测的水平，Northern blot分析显示。与盐水处理的对照组相比，全身给药PCP （7.5 mg/kg，皮下（s.c））显著提高了产后32天和50天丘脑prt6 mRNA的表达，但在产后8、13、20或24天则没有。在PD 50时，另一种NMDA受体拮抗剂二唑西平（0.5 mg/kg, s.c）和一种拟精神分裂症多巴胺激动剂甲基苯丙胺（4.8 mg/kg, s.c）模拟了丘脑prt6 mrna水平的显著增加，而D2多巴胺受体拮抗剂氟哌啶醇在没有自身作用的情况下部分抑制了PCP对丘脑prt6表达的影响。这些数据表明，prt6可能通过转录本中长链非编码RNA或microrna靶基因的失调，参与药物性精神分裂症样症状和精神分裂症发病的病理生理过程。
Schizophrenia and similar psychoses induced by NMDA-type glutamate receptor antagonists, such as phencyclidine (PCP) and ketamine, usually develop after adolescence. Moreover, adult-type behavioral disturbance following NMDA receptor antagonist application in rodents is observed after a critical period at around 3 postnatal weeks. These observations suggest that the schizophrenic symptoms caused by and psychotomimetic effects of NMDA antagonists require the maturation of certain brain neuron circuits and molecular networks, which differentially respond to NMDA receptor antagonists across adolescence and the critical period. From this viewpoint, we have identified a novel developmentally regulated phencyclidine-responsive transcript from the rat thalamus, designated as prt6, as a candidate molecule involved in the above schizophrenia-related systems using a DNA microarray technique. The transcript is a non-coding RNA that includes sequences of at least two microRNAs, miR132 and miR212, and is expressed strongly in the brain and testis, with trace or non-detectable levels in the spleen, heart, liver, kidney, lung and skeletal muscle, as revealed by Northern blot analysis. The systemic administration of PCP (7.5 mg/kg, subcutaneously (s.c.)) significantly elevated the expression of prt6 mRNA in the thalamus at postnatal days (PD) 32 and 50, but not at PD 8, 13, 20, or 24 as compared to saline-treated controls. At PD 50, another NMDA receptor antagonist, dizocilpine (0.5 mg/kg, s.c.), and a schizophrenomimetic dopamine agonist, methamphetamine (4.8 mg/kg, s.c.), mimicked a significant increase in the levels of thalamic prt6 mRNAs, while a D2 dopmamine receptor antagonist, haloperidol, partly inhibited the increasing influence of PCP on thalamic prt6 expression without its own effects. These data indicate that prt6 may be involved in the pathophysiology of the onset of drug-induced schizophrenia-like symptoms and schizophrenia through the possible dysregulation of target genes of the long non-coding RNA or microRNAs in the transcript.
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影响因子：
2.5
作者：
Sato, D;Umino, A;Nishikawa, T
通讯作者：
Nishikawa, T
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影响因子：
4.5
作者：
Kim, Albert H.;Reimers, Mark;Mahera, Brion;Williamson, Vernell;McMichael, Omari I.;McClay, Joseph L.;van den Oord, Edwin J. C. G.;Riley, Brien P.;Kendler, Kenneth S.;Vladimirov, Vladimir I.
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Vladimirov, Vladimir I.
影响因子：
12.3
作者：
Perkins DO;Jeffries CD;Jarskog LF;Thomson JM;Woods K;Newman MA;Parker JS;Jin J;Hammond SM
通讯作者：
Hammond SM
影响因子：
7.6
作者：
Clinton, SM;Meador-Woodruff, JH
通讯作者：
Meador-Woodruff, JH
影响因子：
4.7
作者：
Matsuo, R;Murayama, A;Inokuchi, K
通讯作者：
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