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Zinc Deficiency Impairs Retinoic Acid-Induced Differentiation of Human Neurons

Title: Zinc Deficiency Impairs Retinoic Acid-Induced Differentiation of Human Neurons.
Name(s): Gower-Winter, Shannon Dooies, author
Levenson, Cathy W., professor directing thesis
Ilich-Ernst, Jasminka, committee member
Eckel, Lisa, outside committee member
Department of Nutrition, Food, and Exercise Science, degree granting department
Florida State University, degree granting institution
Type of Resource: text
Genre: Text
Issuance: monographic
Date Issued: 2008
Publisher: Florida State University
Place of Publication: Tallahassee, Florida
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: 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.
Identifier: FSU_migr_etd-4085 (IID)
Submitted Note: 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.
Degree Awarded: Spring Semester, 2008.
Date of Defense: March 19, 2008.
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
Bibliography Note: Includes bibliographical references.
Advisory Committee: Cathy W. Levenson, Professor Directing Thesis; Jasminka Ilich-Ernst, Committee Member; Lisa Eckel, Outside Committee Member.
Subject(s): Nutrition
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Owner Institution: FSU

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Gower-Winter, S. D. (2008). Zinc Deficiency Impairs Retinoic Acid-Induced Differentiation of Human Neurons. Retrieved from