Insulin-like growth factor system in glial cells

Abstract

As an intrinsic part of the normal operative CNS, glial cells perform a plethora of functions. They comprise a large fraction of the brainís cell population and their presence provides structure support, helping to mold physiologically functional components, such as the blood-brain barrier and myelin sheaths. Glial expression of factors influencing cellular growth, differentiation and survival, together with factors regulating immunological processes are of great importance and overwhelmingly complex. Elucidating mechanisms involved in governing regulation of such processes is important for understanding cellular events and crucial in the case of pathologies, where there is often urgency for therapeutic interventions. The pathological situation known as multiple sclerosis is a demyelinating disease of the CNS. Therapeutic strategies attempt to intervene in a variety of mechanisms associated with MS. One possible strategy involves the application of growth factors aimed at repairing damage caused by immune invasion and replenishing precursor cell populations. Because IGF-1 has the potential to stimulate myelin production and proliferation of oligodendrocyte precursor cells this factor provides a promising tool in treating demyelinating diseases. However, the complex nature of IGF-1 regulation is not completely understood. In order to design a rational approach to obtain the desired effects, our knowledge of the IGF-system in the CNS must be extended. This thesis describes studies, aimed at elucidating the involvement of IGF and the regulatory IGFBPs on glial cell functions, with emphasis on astrocytes.