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The synthetic NCAM mimetic peptide FGL mobilizes neural stem cells in vitro and in vivo

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Abstract

The neural cell adhesion molecule (NCAM) plays a role in neurite outgrowth, synaptogenesis, and neuronal differentiation. The NCAM mimetic peptide FG Loop (FGL) promotes neuronal survival in vitro and enhances spatial learning and memory in rats. We here investigated the effects of FGL on neural stem cells (NSC) in vitro and in vivo. In vitro, cell proliferation of primary NSC was assessed after exposure to various concentrations of NCAM or FGL. The differentiation potential of NCAM- or FGL-treated cells was assessed immunocytochemically. To investigate its influence on endogenous NSC in vivo, FGL was injected subcutaneously into adult rats. The effects on NSC mobilization were studied both via non-invasive positron emission tomography (PET) imaging using the tracer [18F]-fluoro-l-thymidine ([18F]FLT), as well as with immunohistochemistry. Only FGL significantly enhanced NSC proliferation in vitro, with a maximal effect at 10 μg/ml. During differentiation, NCAM promoted neurogenesis, while FGL induced an oligodendroglial phenotype; astrocytic differentiation was neither affected by NCAM or FGL. Those differential effects of NCAM and FGL on differentiation were mediated through different receptors. After FGL-injection in vivo, proliferative activity of NSC in the subventricular zone (SVZ) was increased (compared to placebo-treated animals). Moreover, non-invasive imaging of cell proliferation using [18F]FLT-PET supported an FGL-induced mobilization of NSC from both the SVZ and the hippocampus. We conclude that FGL robustly induces NSC mobilization in vitro and in vivo, and supports oligodendroglial differentiation. This capacity renders FGL a promising agent to facilitate remyelinization, which may eventually make FGL a drug candidate for demyelinating neurological disorders.

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Acknowledgments

This research work has been supported by the European Community’s Seventh Framework Programme, project number 2,780,006, “NeuroFGL”. We thankfully acknowledge further support by Köln Fortune Program/Faculty of Medicine, University of Cologne, Germany, to SB (253/2012).

Disclosures

The authors indicate no potential conflicts of interest.

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Authors and Affiliations

  1. Department of Neurology, University Hospital of Cologne, Kerpener Strasse 62, 50924, Cologne, Germany

    Rebecca Klein, Stefan Blaschke, Meike Keuters, Joerg Hucklenbroich, Gereon Rudolf Fink, Michael Schroeter & Maria Adele Rueger

  2. Max Planck Institute for Neurological Research, Cologne, Germany

    Rebecca Klein, Bernd Neumaier, Heike Endepols & Rudolf Graf

  3. Cognitive Neurology Section, Institute of Neuroscience and Medicine Research Centre Juelich, Juelich, Germany

    Gereon Rudolf Fink, Michael Schroeter & Maria Adele Rueger

  4. Enkam Pharmaceuticals A/S, Copenhagen, Denmark

    Morten Albrechtsen & Stephen Rees

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  1. Rebecca Klein
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Correspondence to Maria Adele Rueger.

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The two first authors (Rebecca Klein and Stefan Blaschke) contributed equally to this work, thus they share first authorship.

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Klein, R., Blaschke, S., Neumaier, B. et al. The synthetic NCAM mimetic peptide FGL mobilizes neural stem cells in vitro and in vivo. Stem Cell Rev and Rep 10, 539–547 (2014). https://doi.org/10.1007/s12015-014-9512-5

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