Impact of Erb-B Signaling on Myelin Repair in the CNS Following Virus-Induced Damage

Project: Research project

Project Details

Description

PUBLIC ABSTRACT

Individuals with multiple sclerosis (MS) experience loss of myelin in the central nervous system (CNS). Development of MS is often associated with a viral infection, thus highlighting the importance of examining the role of viruses in the demyelination process. Our long-term goal is to explore the possibilities of intervening in the demyelination processes in the CNS related to infectious and environmental agents and minimizing host tissue damage. Myelin is responsible for assisting the axon (part of the neuron) in transmitting impulses, thereby allowing an individual to function (for example, allowing a person to walk). Many of the treatments available to MS patients focus on controlling or stopping damage to myelin. While it is admirable to control myelin loss, it is unlikely that function will be retained unless myelin can be repaired. The goal of these studies is to understand what processes must be triggered to allow for enhanced repair of myelin. The body is capable of repairing myelin; the peripheral nervous system (PNS) is quite proficient at myelin repair. The CNS (that is, the brain and the spinal cord) is less effective at myelin repair, probably due to the fact that the cells responsible for myelination (the oligodendrocytes) are very different from the cells in the PNS that make myelin (Schwann cells). In the PNS, neuregulins are key proteins involved in myelination. Neuregulins interact with molecules on myelinating cells (erbB receptors) and myelination can be increased. We will examine the role of neuregulins and their receptors in the CNS in an animal model of MS to determine if we can experimentally manipulate them to increase myelin repair. Our goal is to lay the foundation for therapies aimed at myelin repair.

In the studies in this proposal, we will use mice that are infected with Theiler's murine encephalomyelitis virus (TMEV) to determine the processes that are invoked immediately after virus infection of the CNS. The immediate objective of this proposal is to define neuregulin-mediated interactions that enhance myelin preservation/repair in the spinal cord following TMEV injection through testing the hypothesis that neuregulins invoke erbB signaling and protect the CNS by limiting Theiler's virus-induced pathology and triggering myelin repair processes. Development of MS is often associated with a viral infection, thus highlighting the importance of examining the role of viruses in the demyelination process. Our long-term goal is to explore the possibilities of intervening in the demyelination processes in the CNS related to infectious and environmental agents and minimizing host tissue damage.

StatusFinished
Effective start/end date1/1/0612/31/06

Funding

  • U.S. Department of Defense: $892,949.00

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