ACE activity in blood and brain axis in an animal model for schizophrenia: Effects of dopaminergic manipulation with antipsychotics and psychostimulants

Abstract

Objectives: Angiotensin I-converting enzyme (ACE) was initially correlated with schizophrenia (SCZ) in studies showing a correlation of ACE increased enzyme activity with memory impairments. Possible role for ACE in SCZ was also suggested by ACE activity interaction with dopaminergic mechanisms to modulate abnormalities of sensorimotor gating. In addition, we have demonstrated higher ACE activity in blood of SCZ subjects, its implication in cognitive performance in SCZ and its power as a predictor for SCZ diagnosis.

Methods: ACE activity was determined in the serum and in selected brain regions of an animal model presenting SCZ-like behaviour, before and after the treatment with typical and atypical antipsychotics, and also in the serum of animals receiving the psychostimulants amphetamine/lisdexamphetamine.

Results: Dopaminergic manipulations with antipsychotics and psychostimulants influenced the ACE activity, but with no correlation with the animal blood pressure.

Conclusions: The validity of measuring ACE activity in animal blood to predict activity in the CNS, as well as the lack of correlation between the activity and blood pressure, before and after the treatment with antipsychotics, were confirmed here. Correlations of the present findings with data from clinical studies also strengthen the value of this animal model for studying several aspects of SCZ.

Keywords:

• ACE enzyme activity
• animal model
• blood pressure
• central nervous system
• schizophrenia

Acknowledgments

We also thank the executive secretary Rosemary Alves de Oliveira for the great administrative support and Marcela Nering for the extraordinary technical assistance.

Statement of interest

No potential conflict of interest was reported by the authors.

Role of the funding source

João V. Nani and Caroline D. Mas both receive fellowships from CNPq. Camila M. Yonamine was recipient of a fellowship from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo). Mirian AF Hayashi is supported by FAPESP (Proc. No. 2013/13392-4 and 2017/02413-1), CAPES and CNPq (Proc. No. 477760/2010-4; 557753/2010-4; 508113/2010-5; 311815/2012-0; 475739/2013-2). Dr. MAF Hayashi is also the recipient of a fellowship from CNPq (311815/2012-0 and 309337/2016-0). This study was also financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brazil (CAPES) - Finance Code 001.

Additional information

Funding

The authors would like to give thanks for access to the spectrofluorimeter F7000 (Hitachi, Tokyo, Japan) used at the Department of Biophysics, UNIFESP/EPM, and Biosciences (UNIFESP-Santos) for access to the F-7000 Fluorimeter (Hitachi, Tokyo, Japan) supported by FAPESP (Proc. no. 09/54598).