Leukemia inhibitory factor promotes olfactory sensory neuronal survival via phosphoinositide 3-kinase pathway activation and Bcl-2

Authors

  • Cheil Moon,

    Corresponding author
    1. Department of Oral Anatomy and Neurobiology, Kyungpook National University School of Dentistry, Daegu, Republic of Korea
    2. Brain Science and Engineering Institute, Kyungpook National University, Daegu, Republic of Korea
    3. Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland
    • Department of Oral Anatomy and Neurobiology, Kyungpook National University School of Dentistry, 188-1 Samdeok Dong, Jung-Gu, Daegu, 700-412 Republic of Korea
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  • Bridget Q. Liu,

    1. Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • So Yeun Kim,

    1. Department of Oral Anatomy and Neurobiology, Kyungpook National University School of Dentistry, Daegu, Republic of Korea
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  • Esther J. Kim,

    1. Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • Yun Ju Park,

    1. Department of Oral Anatomy and Neurobiology, Kyungpook National University School of Dentistry, Daegu, Republic of Korea
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  • Joo-Yeon Yoo,

    1. Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
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  • Hyung Soo Han,

    1. Brain Science and Engineering Institute, Kyungpook National University, Daegu, Republic of Korea
    2. Department of Physiology, Kyungpook National University School of Medicine, Daegu, Republic of Korea
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  • Yong Chul Bae,

    1. Department of Oral Anatomy and Neurobiology, Kyungpook National University School of Dentistry, Daegu, Republic of Korea
    2. Brain Science and Engineering Institute, Kyungpook National University, Daegu, Republic of Korea
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  • Gabriele V. Ronnett

    Corresponding author
    1. Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland
    2. Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
    • Departments of Neuroscience and Neurology, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205
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Abstract

Leukemia inhibitory factor (LIF), a neuropoietic cytokine, has been implicated in the control of neuronal development. We previously reported that LIF plays a critical role in regulating the terminal differentiation of olfactory sensory neurons (OSNs). Here, we demonstrate that LIF plays a complementary role in supporting the survival of immature OSNs. Mature OSNs express LIF, which may be elaborated in a paracrine manner to influence adjacent neurons. LIF null mice display more apoptotic immature neurons than do their wild-type littermates. LIF treatment of dissociated OSNs in vitro significantly reduces the apoptosis of immature OSNs. Double immunocytochemical analysis indicates that the survival of immature OSNs is dependent on the presence of LIF. LIF activates the phosphoinositide 3-kinase (PI3K) pathways and induces the expression of the antiapoptotic molecule Bcl-2 in OSNs, whereas inhibition of the PI3K pathway blocks LIF-dependent OSN survival and Bcl-2 induction. Thus, LIF plays a central role in maintaining the size and integrity of the population of immature neurons within the olfactory epithelium; this population is critical to the rapid recovery of olfactory function after injury. LIF may play a similar role elsewhere in the CNS and thus be important for manipulation of stem cell populations for therapeutic interventions. © 2008 Wiley-Liss, Inc.

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