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Phagocytic Removal of Neuronal Debris by Olfactory Ensheathing Cells Enhances Neuronal Survival and Neurite Outgrowth via p38MAPK Activity

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Abstract

Compelling evidence from animal models and clinical studies suggest that transplantation of olfactory ensheathing cells (OECs), specialized glia in the olfactory system, combined with specific training may be therapeutically useful in the central nervous system (CNS) injuries and neurodegenerative diseases. The unique function of OECs could mainly attribute to both production of cell adhesion molecules and secretion of growth factors in OECs, which support neuron survival and neurite outgrowth. However, little is known about whether engulfment of neuronal degenerative debris by OECs also equally contributes to neuronal survival and neurite outgrowth. Furthermore, the molecular mechanisms responsible for neuronal degenerative corpses' removal remain elusive. Here, we used an in vitro model of primary culture of spinal cord neurons to investigate the effect of engulfment of degenerative neuron debris by OECs on neuronal survival and neurite outgrowth and the possible molecular mechanisms. Our results showed that OECs can engulf an amount of degenerated neuron debris, and this phagocytosis can make a substantial contribution to neuron growth, as demonstrated by increased number of neurons with longer neurite length and richer neurite branches when compared with the combination of neuron debris and OEC conditioned medium (OECCM). Moreover, p38 mitogen-activated protein kinase (p38MAPK) signaling pathway may mediate the OEC engulfment of debris because the p38MAPK-specific inhibitor, SB203580, can abrogate all the positive effects of OECs, including clearance of degenerated neuron debris and generation of bioactive molecules, indicating that p38MAPK is required for the process of phagocytosis of the neuron debris. In addition, the OEC phagocytic activity had no influence on its generation of bioactive molecules. Therefore, these findings provide new insight into further investigations on the OEC role in the repair of traumatic CNS injury and neurodegenerative diseases.

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Acknowledgments

This work was supported by the Natural Science Foundation of China (grant nos. 81371411, 81071486, 81171137, and 81372056).

Conflict of Interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Spine Surgery, Hong Hui Hospital, Xi’an Jiaotong University College of Medicine, Shaanxi, 710054, China

    Bao-Rong He

  2. Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, 710032, China

    Song-Tao Xie

  3. Institute of Neurosciences, The Fourth Military Medical University, Xi’an, China

    Ming-Mei Wu

  4. Department of Orthopaedics, Hong Hui Hospital, Xi’an Jiaotong University College of Medicine, Shaanxi, 710054, China

    Ding-Jun Hao

  5. Clinic Stem Cell Research Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200217, China

    Hao Yang

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  1. Bao-Rong He
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  2. Song-Tao Xie
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Correspondence to Ding-Jun Hao or Hao Yang.

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He, BR., Xie, ST., Wu, MM. et al. Phagocytic Removal of Neuronal Debris by Olfactory Ensheathing Cells Enhances Neuronal Survival and Neurite Outgrowth via p38MAPK Activity. Mol Neurobiol 49, 1501–1512 (2014). https://doi.org/10.1007/s12035-013-8588-2

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