The Florey Institute for Neuroscience and Mental Health, Parkville, Australia.
The Department of Psychiatry, The University of Melbourne, Parkville, Australia.
World J Biol Psychiatry. 2020 Jun;21(5):402-408. doi: 10.1080/15622975.2018.1548781. Epub 2019 Jan 14.
ATPase Type 13A4 (ATP13A4) is a cation-transporting, P-type ATPase that has been implicated in neurodevelopmental disorders. Our recent microarray study reported a significant increase in ATP13A4 mRNA levels in Brodmann's area (BA) nine in subjects with schizophrenia compared to controls. Following this discovery we have sought to determine whether ATP13A4 expression was altered in other regions of the CNS that are affected in schizophrenia. Quantitative PCR was used to measure the levels of ATP13A4 in BA 44 and BA 8, collected post-mortem, from 30 subjects with schizophrenia and 30 non-psychiatric control subjects. To address the potential confound of antipsychotic medication on our data, qPCR was used to measure Atp13a4 levels in rats treated with haloperidol. There was a 2.6-fold increase in ATP13A4 expression ( < 0.001) in BB 44 from subjects with schizophrenia. Results from BA 8 were less clear. ATP13A4 levels were not affected by antipsychotic treatment. Our findings suggest ATP13A4 is involved in the pathophysiology of schizophrenia. The increase in ATP13A4 contrasts genetic studies that report ATP13A4 gene deletions in patients with schizophrenia. A greater understanding of the function of ATP13A4 in the CNS may lead to improved treatment strategies for the symptoms of schizophrenia.
ATP 酶类型 13A4(ATP13A4)是一种阳离子转运的 P 型 ATP 酶,与神经发育障碍有关。我们最近的基因芯片研究报告称,与对照组相比,精神分裂症患者布罗德曼脑区(BA)9 中的 ATP13A4mRNA 水平显著增加。在这一发现之后,我们试图确定 ATP13A4 在精神分裂症患者中枢神经系统(CNS)其他受影响的区域是否发生改变。定量 PCR 用于测量 30 名精神分裂症患者和 30 名非精神病对照者死后采集的 BA44 和 BA8 中 ATP13A4 的水平。为了解决抗精神病药物对我们数据的潜在干扰,qPCR 用于测量用氟哌啶醇治疗的大鼠中的 Atp13a4 水平。与对照组相比,精神分裂症患者的 BB44 中 ATP13A4 的表达增加了 2.6 倍( < 0.001)。BA8 的结果不太明确。ATP13A4 水平不受抗精神病药物治疗的影响。我们的研究结果表明,ATP13A4 参与了精神分裂症的病理生理学。与报告精神分裂症患者 ATP13A4 基因缺失的遗传研究形成鲜明对比的是,ATP13A4 的增加。更深入地了解 ATP13A4 在中枢神经系统中的功能可能会导致改善精神分裂症症状的治疗策略。