Role of IP3 and ryanodine receptors in the hippocampus development

• Grant number: 12/24910-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2013
• End date: October 31, 2014
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Alexandre Hiroaki Kihara
• Grantee: Marcio Vinicius Damico
• Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated research grant: 08/55210-1 - Cell coupling in the arc of life: development, adaptation and degeneration of the nervous system, AP.JP

Abstract

During the development of Central Nervous System (CNS), the cortical formation occurs from the proliferation and migration of neurons from ventricular (VZ) and subventricular zones (SVZ), located nearby to the lateral ventricle. The hippocampal formation, a region related to memory and learning, is also shaped of neurons from VZ and SVZ. As in other parts of the CNS, cell signaling in the hippocampus, VZ and SVZ are regulated by the intracellular variation of calcium concentration, which is dependent on both external calcium and intracellular stores located in the organelles, such as endoplasmic reticulum and mitochondria. These organelles express receptors of inositiol 1,4,5-trifosfato (IP3R) and of ryanodine (RyR) that control the release of calcium to cytosol. The goal of this project is to evaluate the participation of these receptors and, consequently, the role of intracellular calcium in the development of hippocampus. For this porpuse, the RyR and IP3R of 16-days embryo will be blocked with specific blockers by intraventricular injection. After blockade, possible alterations will be evaluated, such as i) cell proliferation using common markers like BrdU and Ki67, ii) synaptogenesis, by evaluating of expression of genes involved in chemical synapses, including synapsin and synaptophysin, and electrical synapses, such as Cx36 and Cx45. We will combine techniques, like immunohistochemistry, real time PCR, immunoblotting and morphometric analysis to provide an in-depth approach on this fundamental, yet not fully explored, scientific question. Considering that alterations in hippocampus development have been associated to the uprising of conditions like Alzheimer's disease, temporal lobe epilepsy and depression, our proposal is justified by the careful examination of aspects related to these changes. It is important highlight that all the equipments and reagents for the complete realization of this project are available in the Laboratório de Neurobiologia at UFABC. This proposal will count on collaboration of of undergraduated and graduated students, and post-docs as well. Moreover, this project is supported by the project Jovem Pesquisador FAPESP 2008/55210-1.