Some of the material in is restricted to members of the community. By logging in, you may be able to gain additional access to certain collections or items. If you have questions about access or logging in, please use the form on the Contact Page.
Neurogenesis is the process of stem cell proliferation, survival, and differentiation. Recent research has confirmed the presence of ongoing neurogenesis throughout life in humans. This fact has led to vast interest in the mechanisms that underlie this process. Manipulation of adult neurogenesis has the potential to enhance the treatment of a multitude of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and depression as well as injury and stroke. Previous work has shown that the essential trace metal zinc regulates neuronal precursor proliferation and survival. Thus, this work is based on the central hypothesis that zinc is also needed for neuronal differentiation. Furthermore we proposed that transforming growth factor signaling may be involved in the zinc regulated mechanisms of differentiation. Zinc deficiency (ZD; 0.4µM) impaired the ability of neuronal precursor cells (NT2) to differentiate into mature neurons (NT2-N) when exposed to 2 wks of 10µM retinoic acid (RA), as measured by the early neuronal marker TuJ1. Additionally, we demonstrated a differential regulation of Transforming Growth Factor Beta (TGF-β) receptor isoforms type I (RI) and II (RII) under zinc deficient (0.4µM) conditions in NT2 cells undergoing RA-induced differentiation. Measurements of TGF-β RI and RII in zinc adequate (ZA; 2.5µM) differentiated NT2-N neurons showed that neither receptor isoform was expressed in these cells. TGF-β RI was up-regulated in NT2-N cells in response to ZD (0.4µM) however, while TGF-β RII remained down-regulated under ZD (0.4µM) conditions, as demonstrated via TGF-β RI and RII immunocytochemistry. These data confirmed that ZD (0.4µM) does impair RA-induced differentiation of human NT2 neuronal cells. There is also evidence that a differential regulation of the TGF-β receptor I and II isoforms may be involved in this mechanism, as the loss of RII expression in ZD (0.4µM) NT2-N cells could be responsible for a decline in TGF-β signaling in these cells and thus an attenuated cellular response to TGF-β responsive genes. This research suggests an important role for TGF-β and the trace metal zinc in regulating neuronal differentiation, and helps to improve understanding of adult neurogenesis in the human brain.
A Thesis submitted to the Department of Nutrition, Food and Exercise Sciences in partial fulfillment of the requirements for the degree of Master of Science.
Includes bibliographical references.
Cathy W. Levenson, Professor Directing Thesis; Jasminka Ilich-Ernst, Committee Member; Lisa Eckel, Outside Committee Member.
Florida State University
Use and Reproduction
This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). The copyright in theses and dissertations completed at Florida State University is held by the students who author them.