Role of purinergic receptors in an animal model of hippocampal immaturity

• Grant number: 24/17556-6
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: April 01, 2025
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Alexander Henning Ulrich
• Grantee: Natalia Turrini
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases, AP.TEM

Abstract

Bipolar disorder (BD) represents a psychiatric condition with a high degree of disability and few diagnostic and treatment tools due to the poorly elucidated biomolecular mechanism and the overlap of symptoms with other disorders, making it extremely important to better understand the pathophysiology of BD. The neurobiological factors involved in this disorder include mechanisms of neuroinflammation, mitochondrial dysfunction, excitotoxicity, and impairment of neurogenesis and neuronal differentiation. Additionally, cellular immaturity in the hippocampal neurogenic region of the dentate gyrus is one of the most well-characterized endophenotypes in BD and has been related to decreased activity of the enzyme CaMKII-¿, whose functions encompass numerous processes in maintaining synaptic integration. The toxic microenvironment generated by the pathophysiology of BD leads to neurodegeneration processes, aggravating neurogenic dysfunction. Purinergic receptors play roles in processes that appear altered in BD, such as neurogenesis and neuroinflammation, and have direct and indirect relationships with the enzyme CaMKII-¿ through calcium signaling, mainly the P2X7 receptor. Therefore, understanding the mechanisms by which these factors communicate and relate in the pathological situation of BD constitutes an extremely interesting chain that can reveal potential biomarkers for better diagnosis and/or latent therapeutic targets.