Research on receptor tyrosine kinase induced by catecholaminergic agonist in rat brain

儿茶酚胺激动剂诱导大鼠脑内受体酪氨酸激酶的研究

• 批准号: 10470200
• 负责人: NUMACHI Yohtaro
• 金额: $ 6.27万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470200/
• 关键词: stimulant-induced psychosis; reverse tolerance; tyrosine kinase; methamphetamine; neuronal plasticity; メタンフェタミン

Among catecholaminergic agonist, methamphetamine (MAP) is the most abused drug in Japan. MAP causes a severe psychotic state which resembles schizophrenia (Sato, Numachi, 1992). Because vulnerability to relapse in MAP-induced psychosis lasts for a long time, enduring changes in neural function is expected to underlie MAP psychosis. Reverse tolerance phenomenon, observed in MAP-treated animals, provides a good animal model for MAP psychosis as well as schizophrenia (Numachi, 1998).By collaboration with Dr. T. Nishikawa (NCNP, Japan) we found that mRNA for rEphA7, one of receptor tyrosine kinases' family, increased in rat brain by acute MAP treatment, using RNA arbitrary-primed PCR method. rEphA7 plays an important role in axonal guidance and synaptic reorganization in brain. To clarify if abnormal synapse formation, related to reverse tolerance, is induced by MAP via rEphA7, we examined brain expression of rEphA7 in brain of MAP-treated rats using in situ hybridization. So far we observed mRNA for rEphA6 is increased in rat prefrontal cortex by MAP.

在儿茶酚胺能激动剂中，甲基苯丙胺（MAP）是日本滥用最多的药物。MAP导致类似精神分裂症的严重精神状态（Sato, Numachi, 1992）。由于MAP诱导的精神病易复发持续很长时间，神经功能的持续变化可能是MAP精神病的基础。在MAP治疗动物中观察到的反向耐受现象，为MAP精神病和精神分裂症提供了良好的动物模型（Numachi, 1998）。通过与T. Nishikawa博士（NCNP, Japan）合作，我们使用RNA任意引物PCR方法发现，急性MAP治疗大鼠脑中rEphA7（受体酪氨酸激酶家族之一）的mRNA增加。rEphA7在脑内轴突引导和突触重组中起重要作用。为了明确MAP是否通过rEphA7诱导与反向耐受相关的异常突触形成，我们使用原位杂交技术检测了MAP处理大鼠大脑中rEphA7的表达。到目前为止，我们通过MAP观察到大鼠前额皮质中rEphA6 mRNA的表达增加。

项目成果

戸田重誠 他: "精神医学レビューNo.33 精神障害における心因(分担執筆)"ライフ・サイエンス. 6 (2000)

Shigemasa Toda 等人：“精神病学评论第 33 期精神障碍的心理原因（合著者）”生命科学 6（2000 年）。

Sato, M. et al: "The etiology and prophylaxis of schizophrenia based on the stress-vulnerability hypothesis (in Japanese)"Japanese Journal of Clinical Psychiatry. 29. 375-380 (2000)

Sato, M. 等人：“基于应激脆弱性假说的精神分裂症的病因学和预防（日语）”日本临床精神病学杂志。

沼知陽太郎: "分裂病の生物学的脆弱性"精神医学. 42(5). 457-462 (2000)

Yotaro Numachi：“精神分裂症的生物学脆弱性”精神病学 42(5) (2000)。

沼知 陽太郎 他: "興奮剤"日本臨床. 27. 523-526 (1999)

Yotaro Numachi 等：“兴奋剂”日本临床。27. 523-526 (1999)

Sumiko Yoshida et al.: "Impairment of cliff avoidance reaction induced by …"Prog. Neuro-Psychopharmacol. & Biol. Psychat. 22. 1023-1032 (1998)

Sumiko Yoshida 等人：“……引起的悬崖回避反应损伤”Prog. Neuro-Psychopharmacol. 22. 1023-1032 (1998)