Date of Completion
Dr. Stephen Crocker
Elisa Barbarese, Ph.D.
Royce Mohan, Ph.D.
Douglas Oliver, Ph.D.
Nada Zecevic, Ph.D. M.D.
Field of Study
Doctor of Philosophy
The extracellular environment plays an important and crucial role in orchestrating the behaviors of the cells in the central nervous system (CNS). In my thesis work, I studied how the extracellular environment regulates a subset of glial cells, Oligodendrocytes (OLs) and astrocytes. Moreover, I studied the relationship of the astrocyte and the OL, particularly for astrocytes to promote a favorable environment for OL maturation. The extracellular matric (ECM) is composed of a variety of factors, including glycoproteins and secreted extracellular proteins.
In my thesis work, I focused on a subset of glycoproteins: Laminin (Ln), Tenascin-C (TnC), Fibronectin (Fn), and Vitronectin (Vn) and their regulation of astrocytes. As described in chapter 4 of my thesis, I concluded that the ECM differentially regulates astrocytes and their functions through β1 integrin. Additionally, I studied the effect of an extracellular factor, tissue inhibitor of metalloproteinase (TIMP)-1 and its effect on both astrocytes and OLs. In chapter 5 of my thesis, I described how TIMP-1 is important for astrocytic behavior and astrocytes’ ability to respond to injury and inflammation.
Furthermore, I studied the effect of the extracellular environment on OL maturation. First, as described in chapter 6 of my thesis, I studied the direct effect of TIMP-1 on OL maturation and discovered a previously unreported mechanism of TIMP-1 action on OL maturation. I also studied the effect of TIMP-1 on the astrocyte and how it affected OL maturation, specifically through the factors that astrocytes secrete in the absence of TIMP-1. As described in chapter 7 of my thesis, I found that TIMP-1 regulates the factors astrocytes secrete, specifically a Fn fragment that inhibits OL maturation.
In general, my thesis studies focused on the effect of the extracellular environment, particularly the ECM molecules, Ln, TnC, Fn, Vn, and the secreted factor, TIMP-1 on the glial cells, astrocytes’ and OLs’ functions.
Johnson, Kasey Marie, "Extracellular Regulation of Glial Cell Functions" (2015). Doctoral Dissertations. 1002.