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The Journal of Neuroscience, September 15, 2001, 21(18):7161-7170

Leukemia Inhibitory Factor Determines the Growth Status of Injured Adult Sensory Neurons

William B. J. Cafferty¹, Natalie J. Gardiner¹, Isabella Gavazzi², James Powell¹, Stephen B. McMahon¹, John K. Heath³, John Munson⁴, James Cohen², and Stephen W. N. Thompson¹

¹ Centre for Neuroscience Research and ² Medical Research Council Centre for Developmental Neurobiology, Guy's, King's, and St. Thomas' School of Biomedical Science, King's College London, London SE1 1UL, United Kingdom, ³ School of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom, and ⁴ Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida 32610

Conditioning injury to adult mammalian sensory neurons enhances their regeneration potential. Here we show that leukemia inhibitory factor (LIF) is a fundamental component of the conditioning response. Conditioning injury in vivo significantly increases the intrinsic growth capacity of sensory neurons in vitro from LIF+/+ mice. This conditioning effect is significantly blunted in sensory neurons from LIF/ mice. Enhanced growth is rescued in vitro in LIF/ mice by the addition of exogenous LIF, and the effect blocked by human LIF-05, an LIF receptor antagonist. Furthermore, we demonstrate that LIF promotes elongating but not arborizing neurite outgrowth in vitro and is required for normal regeneration of injured adult sensory neurons in vivo. LIF is also functionally protective to peptidergic sensory neurons after nerve damage in vivo. Our results indicate that the alteration in intrinsic growth status of injured sensory neurons depends, at least in part, on LIF.

Key words: leukemia inhibitory factor; gp130; regeneration; conditioning lesion; axotomy; sensory neuron

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21187161-10$05.00/0

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