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:
CreatorsEmailORCIDORCID Put Code
Klein, RebeccaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blaschke, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neumaier, BerndUNSPECIFIEDorcid.org/0000-0001-5425-3116UNSPECIFIED
Endepols, HeikeUNSPECIFIEDorcid.org/0000-0002-6166-4818UNSPECIFIED
Graf, RudolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Keuters, MeikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hucklenbroich, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Albrechtsen, MortenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rees, StephenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fink, Gereon RudolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schroeter, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rueger, Maria AdeleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; DOPAMINE NEURONS; RECEPTOR AGONIST; DENTATE GYRUS; SPINAL-CORD; BRAIN; STROKE; TRANSPLANTATION; PROLIFERATIONMultiple languages
Cell & Tissue Engineering; Cell Biology; Medicine, Research & ExperimentalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/43351

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