Silencing of CaMKII-alpha in a hippocampal cell line as an in vitro model for the immature dentate gyrus neuropsychiatric endophenotype

• Grant number: 17/17972-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2017
• End date: October 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Yahaira Maria Naaldijk Palma
• Grantee: Natalia Turrini
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 12/50880-4 - Stem cells: from basic studies of kinin and purinergic receptor roles towards therapeutical applications, AP.TEM

Abstract

The main feature of bipolar disorder is the pathological humor oscillation between mania and depression. Recently, the study of specific neuropsychiatric biomarkers (endophenotypes) has been an important tool for the understanding of many neuropsychiatric disorders. In bipolar disorder, an important endophenotype is the neuronal immaturity of the dentate gyrus, which was already previously reproduced in a CaMKII-± heterozygous knockout mouse model. However, the mechanisms involved in this condition and its real role in bipolar disorder pathophysiology are still unclear. Therefore, this project aims to reproduce the dentate gyrus dysfunction through the inhibition of the enzyme CaMKII-± in the murine hippocampal cell line HT22 to generate a compatible condition with the one found in the patient's hippocampus. The present study is expected to contribute to the better understanding of molecular and cellular factors involved in this pathological process. (AU)