Study of astrocyte signaling involving response to excitotoxic stimulation

• Grant number: 14/19562-1
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2015
• End date: April 30, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Maria da Graca Naffah Mazzacoratti
• Grantee: Maria da Graca Naffah Mazzacoratti
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Astrocytes form a large population of cells of the mammalian central nervous system (CNS) being part of a large network, connecting to the blood vessels and neurons, filling the space between them. There is also the astrocyte-astrocyte contact, which is mediated by gap-junctions, normally by connexins. The contacts between the astrocyte and the neurons are performed by a highly dynamic structure, which makes astrocytes very important partner of neurons in the organization and functioning of synaptic cleft. However, the role of astrocytes is not limited to support neuronal activity. It is involved in various functions such as glutamate uptake in prevention of excitotoxicity, protection against oxidative stress due to glutathione production, neuroprotection due to the release of adenosine, protection mediated NH4 + toxicity, protection mediated by degradation of ²-amyloid peptides, facilitating repair the blood brain barrier, reducing vasogenic edema following trauma, stabilization of extracellular fluid, limiting the spread of inflammatory cells and molecules in areas of injury, control the ionic balance and thus, reducing seizure threshold. In this context, knowledge of astrocyte signaling, involved in responses related to excitotoxicity, are of fundamental importance. Thus, this project aims to examine in vitro, signaling molecules produced by astrocytes subjected to excitotoxicity. Astrocytes from two kinds of rodents will be explored; a) vulnerable to temporal lobe epilepsy (Wistar rat) and b) resistant to this type of epilepsy (Proechimys animals). In the process, we aim to better understand how the production of inflammatory mediators and markers of cell death and survival may be involved in processes leading to epileptogenesis, thus understanding the function as astrocytes in this process. In addition, innate mechanisms of neuroprotection or promoted by extracellular matrix components will also be studied in vitro. (AU)