Laboratory Of Glial Biology And Myelin Membrane Biogenesis




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Photo of a mature mouse oligodendroglial cell in culture, stained with anti-sulfatide monoclonal antibody and propidium iodide following treatment with SNAP.


Background

My laboratory studies the cellular and molecular events leading to the formation and maintenance of the myelin membrane in the central and peripheral nervous systems. Our current research is focused on (a) the role of calcium in regulating myelin gene expression and oligodendrocyte survival, (b) the role of cytoskeleton in initiating and maintaining myelin membrane formation, (c) the role of axons in survival of mature oligodendrocytes and maintenance of myelin, and (d) analysis of signaling pathways mediating injury and protection of oligodendroglia. Another project in collaboration with Dr. Robert Lisak analyzes effects of cytokines on differentiation and growth factor production by oligodendrocytes in the CNS and Schwann cells in the PNS.

In multiple sclerosis, neurotrauma and a number of neurologic diseases, cells producing nerve insulation (myelin) in the brain, cord and nerves can be directly killed by immune attack or damaged indirectly by released cytokines and other agents such as nitric oxide. Damage could be decreased if ways could be found to protect CNS and PNS glia from indirect damage so that they maintain their insulating membranes and repair or replace these membranes in neighboring damaged areas. Limiting damage to myelin-producing cells at early stages in local attacks may also prevent the onset and progression of damage to axons and their associated nerve cells before that damage becomes irreversible and results in permanent loss of function.
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Who Are We?
Principal Investigator: Joyce A. Benjamins
Contact Info: Phone: (313) 577-1265
Fax: (313) 577-7552
Community of Science Entry: COS Expertise Profile
Publications: Click here to see the PubMed section.
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Where Are We?
Department of Neurology
Wayne State University School of Medicine
421 E. Canfield
Detroit, MI 48201
Lab: Rooms 3109 and 3117 Elliman Clinical Research Building
Office: Balcony by the elevators, 3rd floor Elliman
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What Do We Do?
To characterize the sequence of events leading from exposure to damaging agents outside the cell to changes in reading of genes within the cell, we utilize cultures of mouse oligodendro-glia, the murine oligodendroglial cell line, N20.1 and rat Schwann cells. Various strategies are studied for their effectiveness in preventing death of myelin-producing cells, protecting the ensheathed axons, and reinitiating normal myelin production. Our long-term objective is to identify strategies for protecting these glia from damage and optimizing myelin repair in white matter injury associated with diseases such as multiple sclerosis or with the sequelae of stroke or trauma.

We utilize laser cytometry to define the changes in Ca++ initiated in glia by cytokines, nitric oxide and the glutamate agonist kainate, and compare their effects on myelin membrane sheet retraction and viability. Another project analyzes changes in cytoskeleton and rates of endocytosis, which accompany Ca++ -mediated retraction of oligodendroglial membrane sheets during injury, with focus on endocytosis of glycolipids and proteolipid protein. A third project investigates the role of increased Ca++ in the pathways leading to necrotic or apoptotic cell death and changes in gene expression. Changes in message levels for myelin proteins (MBP, PLP and DDM-20), relevant transcription factors (SCIP, GtX and CREB) and immediate early genes (zif, c-fos and c-jun) are measured by nuclease protection assay or Northern blotting. In parallel experiments we are developing a myelinating co-culture system to examine effects of axons on the responses of myelinating glia to injury. Effects on myelin, glial viability and axonal integrity will be evaluated by immunocytochemical staining. In situ hybridization, RT-PCR and microarray analysis will assess changes in message levels, while changes in protein expression will be analyzed by immunocytochemistry and Western blotting.
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