Departamento de Farmacologia, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), Rua 3 de maio 100, Ed. INFAR, 3rd floor, São Paulo, CEP 04044-020, Brazil.
Department of Psychiatry, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
Sci Rep. 2020 Oct 28;10(1):18513. doi: 10.1038/s41598-020-75616-2.
Nuclear distribution element-like 1 (NDEL1) enzyme activity is important for neuritogenesis, neuronal migration, and neurodevelopment. We reported previously lower NDEL1 enzyme activity in blood of treated first episode psychosis and chronic schizophrenia (SCZ) compared to healthy control subjects, with even lower activity in treatment resistant chronic SCZ patients, implicating NDEL1 activity in SCZ. Herein, higher NDEL1 activity was observed in the blood and several brain regions of a validated animal model for SCZ at baseline. In addition, long-term treatment with typical or atypical antipsychotics, under conditions in which SCZ-like phenotypes were reported to be reversed in this animal model for SCZ, showed a significant NDEL1 activity reduction in blood and brain regions which is in line with clinical data. Importantly, these results support measuring NDEL1 enzyme activity in the peripheral blood to predict changes in NDEL1 activity in the CNS. Also, acute administration of psychostimulants, at levels reported to induce SCZ-like phenotype in normal rat strains, increased NDEL1 enzyme activity in blood. Therefore, alterations in NDEL1 activity after treatment with antipsychotics or psychostimulants may suggest a possible modulation of NDEL1 activity secondary to neurotransmission homeostasis and provide new insights into the role of NDEL1 in SCZ pathophysiology.
核分布元件样 1（NDEL1）酶活性对于神经突发生、神经元迁移和神经发育很重要。我们之前报道过，与健康对照组相比，治疗后的首发精神病和慢性精神分裂症（SCZ）患者的血液中 NDEL1 酶活性较低，而在治疗抵抗性慢性 SCZ 患者中甚至更低，这表明 NDEL1 活性与 SCZ 有关。在此，在经过验证的 SCZ 动物模型中，基线时血液和几个脑区中观察到较高的 NDEL1 活性。此外，长期使用典型或非典型抗精神病药治疗，在该 SCZ 动物模型中报告了 SCZ 样表型逆转的情况下，血液和脑区中的 NDEL1 活性显著降低，这与临床数据一致。重要的是，这些结果支持测量外周血中的 NDEL1 酶活性，以预测中枢神经系统中 NDEL1 活性的变化。此外，在正常大鼠品系中报告的诱导 SCZ 样表型的水平下，急性给予精神兴奋剂会增加血液中的 NDEL1 酶活性。因此，抗精神病药或精神兴奋剂治疗后 NDEL1 活性的改变可能提示神经传递平衡的继发 NDEL1 活性的可能调节，并为 NDEL1 在 SCZ 病理生理学中的作用提供新的见解。
