Type of Document	Thesis
Author	Gower-Winter, Shannon Dooies
Author's Email Address	shannon@neuro.fsu.edu
URN	etd-04142008-142329
Title	Zinc Deficiency Impairs Retinoic Acid-Induced Differentiation of Human Neurons
Degree	Master of Science
Department	Nutrition, Food, and Exercise Science, Department of
Advisory Committee	Advisor Name Title Cathy W. Levenson Committee Chair Jasminka Ilich-Ernst Committee Member Lisa Eckel Committee Member
Keywords	TGF-Beta TGF-Beta Receptors Adult Neurogenesis Hippocampus Dentate Gyrus Subgranular Layer Granule Cell Layer NT2 Post-Mitotic Neurons Retinoic Acid Induced Differentiation Neuronal Differentiation Zinc Deficiency Zinc
Date of Defense	2008-03-19
Availability	unrestricted
Abstract 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.
Files	Filename       Size       Approximate Download Time (Hours:Minutes:Seconds)     28.8 Modem   56K Modem   ISDN (64 Kb)   ISDN (128 Kb)   Higher-speed Access    GowerWinterSThesis.pdf 321.97 Kb 00:01:29 00:00:45 00:00:40 00:00:20 00:00:01