Universität zu Köln

Klein, Rebecca, Blaschke, Stefan, Neumaier, Bernd ORCID: 0000-0001-5425-3116, Endepols, Heike ORCID: 0000-0002-6166-4818, Graf, Rudolf, Keuters, Meike, Hucklenbroich, Joerg, Albrechtsen, Morten, Rees, Stephen, Fink, Gereon Rudolf, Schroeter, Michael and Rueger, Maria Adele (2014). The synthetic NCAM mimetic peptide FGL mobilizes neural stem cells in vitro and in vivo. Stem Cell Rev. Rep., 10 (4). S. 539 - 548. TOTOWA: HUMANA PRESS INC. ISSN 1558-6804

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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 [F-18]-fluoro-l-thymidine ([F-18]FLT), as well as with immunohistochemistry. Only FGL significantly enhanced NSC proliferation in vitro, with a maximal effect at 10 mu g/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 [F-18]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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Klein, Rebecca UNSPECIFIED UNSPECIFIED UNSPECIFIED Blaschke, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Neumaier, Bernd UNSPECIFIED orcid.org/0000-0001-5425-3116 UNSPECIFIED Endepols, Heike UNSPECIFIED orcid.org/0000-0002-6166-4818 UNSPECIFIED Graf, Rudolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Keuters, Meike UNSPECIFIED UNSPECIFIED UNSPECIFIED Hucklenbroich, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Albrechtsen, Morten UNSPECIFIED UNSPECIFIED UNSPECIFIED Rees, Stephen UNSPECIFIED UNSPECIFIED UNSPECIFIED Fink, Gereon Rudolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeter, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Rueger, Maria Adele UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-433511
DOI:	10.1007/s12015-014-9512-5
Journal or Publication Title:	Stem Cell Rev. Rep.
Volume:	10
Number:	4
Page Range:	S. 539 - 548
Date:	2014
Publisher:	HUMANA PRESS INC
Place of Publication:	TOTOWA
ISSN:	1558-6804
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; DOPAMINE NEURONS; RECEPTOR AGONIST; DENTATE GYRUS; SPINAL-CORD; BRAIN; STROKE; TRANSPLANTATION; PROLIFERATION Multiple languages Cell & Tissue Engineering; Cell Biology; Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43351