Astrocyte-derived interleukin-6 promotes specific neuronal differentiation of neural progenitor cells from adult hippocampus

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2010-10-01
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McCloskey, Michael
Blong, Christopher
Bendickson, Lee
Nilsen-Hamilton, Marit
Sakaguchi, Donald
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Sakaguchi, Donald
Director of Biology and Genetics Undergraduate Program and Morrill Professor
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Nilsen-Hamilton, Marit
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Biomedical Sciences

The Department of Biomedical Sciences aims to provide knowledge of anatomy and physiology in order to understand the mechanisms and treatment of animal diseases. Additionally, it seeks to teach the understanding of drug-action for rational drug-therapy, as well as toxicology, pharmacodynamics, and clinical drug administration.

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The Department of Biomedical Sciences was formed in 1999 as a merger of the Department of Veterinary Anatomy and the Department of Veterinary Physiology and Pharmacology.

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Biochemistry, Biophysics and Molecular Biology

The Department of Biochemistry, Biophysics, and Molecular Biology was founded to give students an understanding of life principles through the understanding of chemical and physical principles. Among these principles are frontiers of biotechnology such as metabolic networking, the structure of hormones and proteins, genomics, and the like.

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The Department of Biochemistry and Biophysics was founded in 1959, and was administered by the College of Sciences and Humanities (later, College of Liberal Arts & Sciences). In 1979 it became co-administered by the Department of Agriculture (later, College of Agriculture and Life Sciences). In 1998 its name changed to the Department of Biochemistry, Biophysics, and Molecular Biology.

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Neuroscience
The Graduate Program in Neuroscience is an interdepartmental and interdisciplinary training program at Iowa State University that offers the Master of Science and Doctor of Philosophy degrees. The Neuroscience training program offers a broad spectrum of Neuroscience research opportunities, ranging from the molecular to the cellular to the systems level of analysis. The program includes over 40 faculty from the departments of Biochemistry, Biophysics and Molecular Biology; Biomedical Sciences; Chemical and Biological Engineering; Ecology, Evolution, and Organismal Biology; Food Science and Human Nutrition; Genetics, Development and Cell Biology; Kinesiology; Mechanical Engineering; and Psychology.
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Abstract

The purpose of this study was to investigate the ability of astrocyte-derived factors to influence neural progenitor cell differentiation. We previously demonstrated that rat adult hippocampal progenitor cells (AHPCs) immunoreactive for the neuronal marker, class III β-tubulin (TUJ1) were significantly increased in the presence of astrocyte-derived soluble factors under non-contact co-culture conditions. Using whole cell patch clamp analysis, we observed that the co-cultured AHPCs displayed two prominent voltage-gated conductances - tetraethyl ammonium (TEA)- sensitive outward currents and fast transient inward currents. The outward and inward current densities of the co-cultured AHPCs were approximately 2.5-fold and 1.7-fold greater, respectively, than those of cells cultured alone. These results suggest that astrocyte-derived soluble factors induce neuronal commitment of AHPCs. To further investigate the activity of a candidate neurogenic factor on AHPC differentiation, we cultured AHPCs in the presence or absence of purified rat recombinant interleukin-6 (IL-6). We also confirmed that the astrocytes used in this study produced IL-6 by ELISA and RT-qPCR. When AHPCs were cultured with IL-6 for 6-7 days, the TUJ1-immunoreactive AHPCs and the average length of TUJ1-immunoreactive neurites were significantly increased, compared to the cells cultured without IL-6. Moreover, IL-6 increased the inward current density to a comparable extent as did co-culture with astrocytes, with no significant differences in the outward current density, apparent resting potential, or cell capacitance. These results suggest that astrocyte-derived IL-6 may facilitate AHPC neuronal differentiation. Our findings have important implications for understanding injury-induced neurogenesis and developing cell-based therapeutic strategies using neural progenitors.

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This is the peer reviewed version of the following article: Oh, J., McCloskey, M. A., Blong, C. C., Bendickson, L., Nilsen-Hamilton, M. and Sakaguchi, D. S. (2010), Astrocyte-derived interleukin-6 promotes specific neuronal differentiation of neural progenitor cells from adult hippocampus. J. Neurosci. Res., 88: 2798–2809, which has been published in final form at doi:10.1002/jnr.22447. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.

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Fri Jan 01 00:00:00 UTC 2010
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