Can EBI2 receptor protect brain cells (oligodendrocytes) from dying during disease?

The four major brain-specific cell types in the brain are: (i) neurons, which transmit and process information via electrical signals, (ii) oligodendrocytes, which insulate neuronal axons with fatty sheets called myelin to ensure fast and complete electrical signal transduction, (iii) microglia, which provide defence against potential infections in the brain and, (iv) astrocytes, which provide metabolic support for neurons and ensure their proper functioning, are involved in immune defence and maintain healthy microenvironment in the brain. These cells, and indeed all living cells, have a wide range of proteins called receptors on their surface, which are activated by signalling molecules. EBI2 is one such receptor that plays very important roles in the biology of immune cells, where it regulates antibody production to fight infections. Our research, aims to investigate whether the presence of EBI2 changes during maturation of oligodendrocytes. We will explore whether EBI2 receptor is involved in regulation of physiological functions of oligodendrocytes, such as intercellular signalling or migration, and myelination of neurons.

EBI2 receptor in different brain cells and its role in brain disease.
Fig. 1. EBI2 receptor in different brain cells and its role in brain disease.

So far studies on EBI2 receptor focused on its role in the cells of the immune system such as B cells. Significance of this receptor’s presence and role in the brain has been unknown. Our recent studies suggest that EBI2 and its signalling molecule (oxysterol 7α25HC) may be involved in the onset and progression of brain diseases. Therefore, it is important to learn how functional status of this receptor and its signalling pathway in the brain may modify the progress of these diseases.  Its predictable application for the control of diseases will also be considered.

Our research so far has shown that EBI2 is present on the surface of astrocyte and oligodendrocytes and that it does play a role in the immune function in the brain. EBI2 activation promotes astrocytes migration and attenuates release of harmful pro-inflammatory molecules called cytokines. The EBI2 receptor is also capable of promoting astrocyte responses to infections, by releasing molecules that attract immune cells into the brain to help fight such pathologic conditions. Our findings also indicate, that the EBI2 receptor may be necessary for appropriate and timely myelination of neurons by oligodendrocytes. Activation of EBI2 receptor can also protect the neuronal cells against chemically induced demyelination. The proposed research will allow us to further investigate the function of EBI2 in the brain, specifically in oligodendrocytes, and also, for the first time, will study the function of the receptor in live animals that have been subjected to demyelination.

Findings resulting from this research are important because they will provide new facts on the role of the EBI2 receptor in the brain, and particularly about its regulatory functions in oligodendrocytes. The experiments using the animal model will give us a unique insight into the mechanisms of demyelinating diseases. Knowledge of these mechanisms may pave the path for development of new drug approaches controlling oligodendrocyte function limiting or enhancing processes of myelinisation.

Aleksandra Rutkowska
Department of Laboratory Medicine, Medical University of Gdansk, Debinki 7, Gdansk, Poland

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 665778. Funding granted by the National Science Centre, Poland as part of the Polonez 2 fellowship programme, registration number 2016/21/P/NZ3/00897.

Publication

EBI2 receptor regulates myelin development and inhibits LPC-induced demyelination.
Rutkowska A, Sailer AW, Dev KK
J Neuroinflammation. 2017 Dec 16
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