In the majority of schizophrenia patients, chronic atypical antipsychotic administration produces a significant reduction in or even complete remission of psychotic symptoms such as hallucinations and delusions. However, these drugs are not effective in improving cognitive and emotional deficits in patients with schizophrenia. Atypical antipsychotic drugs have a high affinity for the dopamine D₂ receptor, and a modest affinity for the serotonin 5-HT_2A receptor. The cognitive and emotional deficits in schizophrenia are thought to involve neural networks beyond the classical dopaminergic mesolimbic pathway, however, including serotonergic systems. For example, mutations in the RELN gene, which encodes Reelin, an extracellular matrix protein involved in neural development and synaptic plasticity, are associated with neurodevelopmental disorders such as schizophrenia and autism spectrum disorder. Furthermore, hippocampal Reelin levels are down-regulated in the brains of both schizophrenic patients and in rodent models of schizophrenia. In the present study, we investigated the effect of Reelin microinjection into the mouse hippocampus on behavioral phenotypes to evaluate the role of Reelin in neurodevelopmental disorders and to test a therapeutic approach that extends beyond classical monoamine targets. To model the cognitive and emotional deficits, as well as histological decreases in Reelin-positive cell numbers and hippocampal synaptoporin distribution, a synaptic vesicle protein, offspring that were prenatally exposed to maternal immune activation were used. Microinjections of recombinant Reelin protein into the hippocampus rescued impairments in object memory and anxiety-like behavior and recruited synaptoporin in the hippocampus in offspring exposed to antenatal inflammation. These results suggest that Reelin supplementation has the potential to treat cognitive and emotional impairments, as well as synaptic disturbances, in patients with neurodevelopmental disorders such as schizophrenia.

在大多数精神分裂症患者中，长期服用非典型抗精神病药可使精神病症状（如幻觉和妄想）显着减少甚至完全缓解。但是，这些药物对改善精神分裂症患者的认知和情绪缺陷无效。非典型抗精神病药对多巴胺D ₂受体具有高亲和力，而对血清素5-HT _2A受体具有适度的亲和力。精神分裂症的认知和情绪缺陷被认为涉及神经网络，而神经网络超出了经典的多巴胺能中脑边缘途径，但包括血清素能系统。例如，RELN该基因编码Reelin，Reelin是一种参与神经发育和突触可塑性的细胞外基质蛋白，与精神分裂症和自闭症谱系障碍等神经发育障碍有关。此外，在精神分裂症患者的脑和精神分裂症的啮齿动物模型中，海马Reelin水平被下调。在本研究中，我们调查了将Reelin显微注射到小鼠海马中对行为表型的影响，以评估Reelin在神经发育障碍中的作用，并测试一种超越经典单胺靶标的治疗方法。为了模拟认知和情绪缺陷，以及Reelin阳性细胞数量和海马突触小泡蛋白分布（一种突触小泡蛋白）的组织学降低，使用在产前暴露于母体免疫激活的后代。将重组Reelin蛋白显微注射到海马中可以挽救暴露于产前炎症后代的海马中对象记忆和焦虑样行为的损伤，并在海马中募集突触突触蛋白。这些结果表明，补充Reelin可以治疗患有神经发育障碍（例如精神分裂症）的患者的认知和情感障碍以及突触障碍。