CaMKII-alpha enzyme expression in schizophrenia and its modulation by purinergics

• Grant number: 25/09598-3
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: October 28, 2025
• End date: February 27, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Alexander Henning Ulrich
• Grantee: Maria Victoria Hennadipgil Queiroz
• Supervisor: Francico Ciruela
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Universitat de Barcelona (UB), Spain
• Associated to the scholarship: 24/17748-2 - Assessment of social behavior in a murine model of hippocampal immaturity, BP.IC

Abstract

Schizophrenia is a neuropsychiatric disorder with complex etiology. Itpresents psychotic symptoms, cognitive impairments, and psychosocial challenges. Current therapeutic approaches fail to address all dimensions of the disease, emphasizing the necessity for innovative solutions. This project investigates the expression of CaMKII-¿, a critical enzyme in synaptic plasticity, and its modulation by purinergic receptors, with particular focus on A2A and P2X7 receptors. The research aims to bridge findings across systems through a combined approach of molecular analyses in postmortem human brain samples and functional studies in cell culture models.Human brain samples will be utilized to examine CaMKII-¿ expression in regions associated with neurogenesis, such as the hippocampus, while SH-SY5Y neuroblast cultures will serve to study enzymatic modulation via CamKAR biosensor technology. Lentiviral transfection and targeted purinergic receptor treatments will provide insights into the regulatory effects of A2A and P2X7 activation on neuronal function. Particular attention will be given to calcium signaling pathways and their contribution to neural network organization.The aim of this project is to validate the translational relevance of the CaMKII-¿ heterozygous knockout mouse model for schizophrenia, advancing its potential as a preclinical tool. Further, the study explores purinergic signaling as a promising therapeutic avenue, aiming to uncover novel pharmacological targets. Collaboration with the University of Barcelona will not only facilitate access to specialized resources but also foster interdisciplinary exchange, enriching the scope of the research.This work holds the potential to deepen understanding of schizophrenia's molecular mechanisms, addressing gaps in the field and supporting the development of targeted therapies that enhance patient outcomes. By combining innovative methodologies and international collaboration, this project contributes significantly to the pursuit of more effective interventions for neuropsychiatric disorders.