| Full text | |
| Author(s): |
Oyadomari, William Y.
;
Santiago, Thays C.
;
Basso, Leonardo
;
Oliveira, Vitor
;
Cruz, Fabio C.
;
Nani, Joao, V
;
Hayashi, Mirian A. F.
Total Authors: 7
|
| Document type: | Journal article |
| Source: | Brain Research; v. 1859, p. 8-pg., 2025-04-17. |
| Abstract | |
Elevated angiotensin I-converting enzyme (ACE) activity has been correlated with worse cognitive performance in patients with first-episode psychosis (FEP) and chronic schizophrenia (SZ). In this study, we investigated ACE activity in drug-na & iuml;ve transgenic rats overexpressing the full-length non-mutated human Disrupted-in-Schizophrenia 1 (tgDISC1) compared to wild-type (WT) controls, while we also assessed the effects of long-term treatment with typical antipsychotic haloperidol. Our findings indicated that untreated tgDISC1 rats show elevated serum ACE activity compared to WT animals, which is consistent with clinical observations in drugna & iuml;ve FEP patients. In contrast, baseline ACE activity in the brain of tgDISC1 was generally lower than in WT rats, with the exception of no difference in ACE activity observed in brain regions associated with learning, memory, and reward, such as the hippocampus and nucleus accumbens. Consistent with clinical observations in FEP patients following treatment with antipsychotics, 30-days of daily haloperidol-treatment significantly increased serum ACE activity in blood serum of both tgDISC1 and WT rats. However, ACE responses in brain were markedly different, as haloperidol treatment reduced ACE activity in most brain regions of both rat strains. These results support the existence of a central renin-angiotensin system (RAS) distinct from the peripheral RAS, suggesting that the treatment with a dopamine blocker exerts brain-specific effects on ACE activity, which was essentially opposite to that observed in the periphery. This region-specific alterations observed in cognition-related brain areas (notably with a relative stronger effect size in hippocampus and nucleus accumbens of tgDISC1 compared to WT rats) also suggest a critical interplay among dopamine homeostasis, ACE activity, and cognitive deficits in SZ. Understanding this interplay could help identifying novel biomarkers and/or therapeutic strategies for improving cognitive outcomes in SZ patients. (AU) | |
| FAPESP's process: | 19/13112-8 - Study of molecular and cellular mechanisms involved in mental disorders: clinical and animal models analysis |
| Grantee: | Mirian Akemi Furuie Hayashi |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 20/01107-7 - Study to optimize the use of crotamine as a theranostic in the therapy of human diseases: cancer, metabolic syndrome and renal dysfunction |
| Grantee: | Mirian Akemi Furuie Hayashi |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 19/08287-3 - Effect of crotamine on glucose uptake by brown adipose tissue: evaluation in an experimental model with 18FDG PET |
| Grantee: | Marcelo Tatit Sapienza |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 24/04617-7 - Analysis of oligopeptidase activity in an animal model for schizophrenia |
| Grantee: | Leonardo Basso de Souza |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| FAPESP's process: | 17/02413-1 - Validation of crotamine as a biomarker and evaluation of its potential use in the therapy of human diseases |
| Grantee: | Mirian Akemi Furuie Hayashi |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 14/50891-1 - INCT 2014: Translational Medicine |
| Grantee: | Jaime Eduardo Cecilio Hallak |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 19/09207-3 - Study of molecular and cellular mechanisms in mental disorders |
| Grantee: | João Victor Silva Nani |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 23/07904-4 - Study of molecular and cellular mechanisms of mental disorders: clinical studies and animal models |
| Grantee: | William Yoshio Agliardi Oyadomari |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 22/03297-3 - Exploring the molecular and cellular mechanism(s) underlying neurodevelopmental disorders: investigating the role(s) of Nuclear Distribution Element like-1 (Ndel1) |
| Grantee: | João Victor Silva Nani |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |
| FAPESP's process: | 22/00527-8 - Enzymatic activity of oligopeptidases Ndel1 and/or ACE in plasma or blood serum of patients with Depression |
| Grantee: | Larissa Ribino Parra |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |