精神分裂病における神経情報処理障害の原因となる遺伝子異常の探索

精神分裂症症状发生在青春期之后，精神源性药物诱导精神分裂症样精神病的能力也是年龄依赖性的。此外，实验动物对精神源性药物的行为反应明显依赖于出生后的发育。为了了解精神分裂症神经功能障碍的分子基础，我们研究了不同类型的精神分裂症类药物甲基苯丙胺（methamphetamine， MAP）和苯环利定（phencyclidine， PCP）对发育大鼠大脑基因表达的影响。免疫细胞化学分析c-Fos基因产物的表达作为神经元活性变化的标志，发现在出生后发育过程中，MAP-和pcp -诱导的c-Fos蛋白样免疫反应性在大脑新皮层或纹状体的分布模式发生了显著变化，而在梨状皮层、嗅结节和鼻中隔的分布模式没有发生变化。出生后21 - 23天出现成虫模式。由于map诱导的行为敏化和pcp诱导的成人模式异常行为发生在出生后第三周，这些发现表明，新皮层和/或纹状体中某些神经元回路的成熟可能，至少部分地参与了对这些药物的行为反应的发展。为了进一步探索在这些行为反应成熟中发挥关键作用的某些基因，我们使用RNA任意引物PCR技术研究了新生儿和成人期MAP或pcp诱导的离散脑区基因表达的差异。

Schizophrenic symptoms occur after adolescence and the ability of psychotogenic drugs to induce schizophrenia-like psychosis is also age-dependent. Moreover, the behavioral responses to psychotogenic drugs in experimental animals apparently depend upon postnatal development. To obtain a clue for the molecular basis of neural dyfunction in schizophrenia, we have investigated the effects of different types of schizophrenomimetic drugs, methamphetamine (MAP) and phencyclidine (PCP) on gene expression in the brains of developing rats. Immunocytochemical analysis of expression of c-Fos gene product as a marker for the change in neuronal activity that the distribution patterns of MAP- and PCP-induced c-Fos protein-like immunoreactivity in the brain markedly changed in the neocortex or striatum, but not in the pyriform cortex, olfactory tubercle and septum, during postnatal development. The adult pattern was seen after 21 - 23 postnatal days. Since MAP-induced behavioral sensitization and an adult pattern of PCP-induced abnormal behavior has been observed to occur after the third week of postnatal life, these findings suggest that the maturation of certain neuronal circuits in the neocortex and/or striatum could, at least in part, be involved in the development of the behavioral responses to these drug. To further explore certain genes that play a crucial role in the maturation of these behavioral responses, we have studied differences in MAP- or PCP-induced gene expression in the discrete brain regions between neonatal and adult period using a RNA arbitrarily primed PCR technique.