Effects of schizophrenomimetics on the expression of the CCN1 (CYR 61) gene encoding a matricellular protein in the infant and adult neocortex of the mouse and rat
Effects of schizophrenomimetics on the expression of the CCN1 (CYR 61) gene encoding a matricellular protein in the infant and adult neocortex of the mouse and rat
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DOI：
10.1017/s1461145707007882
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发表时间：
2007-12-01
影响因子：
4.8
通讯作者：
Nishikawa, Toru
中科院分区：
文献类型：
--
作者：
Ito, Takashi;Hiraoka, Shuichi;Nishikawa, Toru
急性全身给药苯环利定（5或10 mg/kg，皮下注射）在小鼠和大鼠出生后56天显著上调了编码分泌的细胞外基质相关蛋白的CCN1基因的新皮质表达，但在出生后第8天，60分钟后没有上调。出生后第8天至第56天之间上调的发育依赖性质似乎与成人型苯环利定诱导的异常行为相似，后者被认为是精神分裂症症状的模型。在年轻成年大鼠中，5、10和20 mg/kg苯环利定（给予s.c）诱导CCN1基因转录物以剂量相关的钟形方式增加，在注射后60分钟，剂量为10 mg/kg时达到最大值。二唑西平（1 mg/kg）和甲基苯丙胺（4.8 mg/kg）等其他模拟精神分裂现象的药物也能显著上调成年大鼠新皮质CCN1基因的表达。这些结果表明，CCN1基因或蛋白可能涉及与通常发生在青春期后的年龄依赖性精神分裂症发病相关的分子级联反应。
The acute systemic administration of a schizophrenomimetic phencyclidine [5 or 10 mg/kg, subcutaneously (s.c.)] markedly up-regulated the neocortical expression of the CCN1 gene encoding a secreted extracellular matrix-associated protein at postnatal day 56, but not at postnatal day 8, after 60 min in the mouse and rat. The development-dependent nature of the up-regulation between postnatal days 8 and 56 seems to be similar to that of the adult type phencyclidine-induced abnormal behaviours, which have been considered to be models of schizophrenic symptoms. In the young adult rat, 5, 10, and 20 mg/kg phencyclidine (given s.c.) induced an increase in the CCN1 gene transcripts in a dose-related and bell-shaped manner with a maximum at the dose of 10 mg/kg, 60 min post-injection. Other schizo-phrenomimetics, dizocilpine (I mg/kg) and methamphetamine (4.8 mg/kg), also caused a prominent up-regulation of the neocortical expression of the CCN1 gene in adult rats. These results indicate that the CCN1 gene or protein could be implicated in a molecular cascade associated with the age-dependent onset of schizophrenia that usually occurs after puberty.