mRNA expression of the P5 ATPase ATP13A4 is increased in Broca’s area from subjects with schizophrenia

Abstract

Objectives: ATPase Type 13A4 (ATP13A4) is a cation-transporting, P₅-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.

Methods: 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.

Results: There was a 2.6-fold increase in ATP13A4 expression (P < 0.001) in BB 44 from subjects with schizophrenia. Results from BA 8 were less clear. ATP13A4 levels were not affected by antipsychotic treatment.

Conclusions: 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.

Keywords:

• ATPase
• Broca’s area
• cortex
• qPCR
• schizophrenia

Acknowledgements

The authors gratefully acknowledge the Victorian Brain Bank as the source of the human post-mortem tissue used in this study and Geoff Pavey for his technical assistance and curation of the human brain tissue.

Statement of interest

None to declare.

Additional information

Funding

This project was supported by the National Health and Medical Research Council [Project Grant 566967] and the Victorian Government’s Operational Infrastructure Support Programme.