https://orcid.org/0000-0002-2706-9118
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Abstract
Introduction
Nuclear distribution element like-1 (Ndel1) is a cytosolic oligopeptidase, which was suggested as a potential biomarker of aberrant neurodevelopment and early stage of schizophrenia (SCZ). The involvement of Ndel1 in neurite outgrowth, neuronal migration and neurodevelopment was demonstrated. Moreover, Ndel1 cleaves neuropeptides, including the endogenous antipsychotic peptide neurotensin, and lower Ndel1 activity was reported in SCZ patients compared with healthy controls (HCs). Changes in brain-derived neurotrophic factor (BDNF) and inflammatory cytokines levels were also implicated in SCZ.
Objective
This preliminary study aimed to investigate the interactions between these immune and neurodevelopmental/neurotrophic biomarkers, namely BDNF and the recently identified SCZ biomarker Ndel1.
Results
We observed lower Ndel1 activity and IL-4 levels, and higher BDNF levels, in plasma of SCZ (N = 23) compared with HCs (N = 29). Interestingly, significant correlation between Ndel1 activity and IL-4 levels was observed in SCZ, while no correlation with any other evaluated interleukins (namely IL-2, IL-8, IL-10 and IL-17A) or BDNF levels was noticed.
Conclusion
Although this hypothesis needs to be further explored for a better understanding of the mechanisms by which these altered pathways are associated to each other in SCZ, we suggest that Ndel1 and the inflammatory marker IL-4 are directly correlated.
Acknowledgments
The authors would like to thank for the access to the spectrofluorimeter F7000 (Hitachi, Tokyo, Japan) used at the Department of Biophysics, UNIFESP/EPM and the Biosciences (UNIFESP-Santos) for the F-7000 Fluorimeter (Hitachi, Tokyo, Japan) supported by FAPESP [Proc. No. 09/54598]. We also thank the executive secretary Rosemary Alves de Oliveira for the great administrative support and Marcela Nering for the extraordinary technical assistance.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Additional information
Funding
Notes on contributors
João V. Nani
João V. Nani: Graduated in Biological Sciences from Universidade Federal de São Paulo (2016) and master's degree in the Psychiatry program at the Universidade Federal de São Paulo (2018). Currently PhD candidate at the Pharmacology program at the Federal University of São Paulo - UNIFESP/EPM. He was a fellow in the Capes Print: Institutional Program for Internationalization at Queens University.
Priscila G. C Almeida
Priscila G. C. Almeida: Graduated in Biomedical Sciences from Universidade Estadual Paulista “Júlio de Mesquita Fillho”. Currently a Master's student at the Pharmacology program at the Federal University of São Paulo - UNIFESP/EPM.
Cristiano Noto
Cristiano Noto: Psychiatrist, Masters (MSc), Doctorate (PhD) and Post Doctorate by Federal University of São Paulo - UNIFESP/EPM. He is a researcher at the Schizophrenia Program (PROESQ) and at the Clinical Neuroscience Laboratory (LiNC). Coordinates the Care Group for Initial Psychosis (GAPi) at UNIFESP. Advisor of the Graduate Program in Psychiatry and Medical Psychology at UNIFESP.
Rodrigo A. Bressan
Rodrigo A. Bressan: Psychiatrist, PhD by the Institute of Psychiatry – King's College London; Prof. Associate Professor of the Department of Psychiatry – UNIFESP. Honorary Professor at the Institute of Psychiatry – King's College London. Coordinator of the Schizophrenia Program – UNIFESP. Coordinator of LiNC – Interdisciplinary Laboratory of Clinical Neurosciences. Coordinator of the Molecular Imaging Group at the Instituto Israelita de Ensino e Pesquisa at the Albert Einstein Hospital. Founder of YMind – Center for the Prevention of Mental Disorders. Organizer of the book “Mental Health at School: what educators should know”, launched in 2015, by the publisher Artmed. Author of high-impact articles and scientific patents and consultant for the formulation of public policies.
Elisa Brietzke
Elisa Brietzke: Advisor of the Postgraduate Program in Psychiatry and Medical Psychology at the Department of Psychiatry at ederal University of São Paulo - UNIFESP/EPM. Now is a full Professor at the Department of Psychiatry, Queen's University, Kingston, ON, Canada. Graduated in Medicine from the Federal University of Rio Grande do Sul (1996) and Medical Residency in Psychiatry from the Federal University of Medical Sciences of Porto Alegre (2007). Master's Degree in the Graduate Program in Medical Sciences at the Federal University of Rio Grande do Sul (UFRGS) (2004), PhD in the Graduate Program in Psychiatry at the Federal University of Rio Grande do Sul (UFRGS) (2010), Post -Doctorate from the Graduate Program in Psychiatry at the Federal University of São Paulo (2012) and Research Fellowship at the University Health Network, University of Toronto, Canada (2017-2018). She was a former president of the Brazilian Association of Bipolar Disorder (ABTB) (2015-2018).
Mirian A. F Hayashi
Mirian A. F. Hayashi: Degree in Pharmacy and Biochemistry from Universidade Estadual de Londrina (1987) PhD in Biological Sciences (Molecular Biology) from the Federal University of São Paulo - UNIFESP/EPM (1997). Post-doctorate (1998-2003) and scientific researcher III at Instituto Butantan (2004-2006). Researcher at Roche's Drug Novel Development Center in Japan, in the fields of pharmacology and biophysics (1989-1993), and consultant at Merck Sharp & Dohme (Division of Neuroscience Research, Terling Parks, UK, 2002-2005). She is currently an associate professor at the Department of Pharmacology at UNIFESP/EPM (where she works since 2006). She was part of the technical chamber of the Technological Innovation Center at UNIFESP and has been committed to transferring technology to the production chain. It has 13 families of patents filed in Brazil and abroad, some of which have already been granted in Europe, USA, Canada and Japan, and others with a signed licensing agreement. Visited Joseph Fourier University (Grenoble, France) (2009) and the Johns Hopkins Hospital (Baltimore, USA) with visiting professor with a Fulbright fellowship (2012).