Aromatic-turmerone induces neural stem cell proliferation in vitro and in vivo.
BACKGROUND
Aromatic (ar-) turmerone is a major bioactive compound of the herb Curcuma longa. It has been suggested that ar-turmerone inhibits microglia activation, a property that may be useful in treating neurodegenerative disease. Furthermore, the effects of ar-turmerone on neural stem cells (NSCs) remain to be investigated.


METHODS
We exposed primary fetal rat NSCs to various concentrations of ar-turmerone. Thereafter, cell proliferation and differentiation potential were assessed. In vivo, naïve rats were treated with a single intracerebroventricular (i.c.v.) injection of ar-turmerone. Proliferative activity of endogenous NSCs was assessed in vivo, by using noninvasive positron emission tomography (PET) imaging and the tracer [(18)F]-fluoro-L-thymidine ([(18)F]FLT), as well as ex vivo.


RESULTS
In vitro, ar-turmerone increased dose-dependently the number of cultured NSCs, because of an increase in NSC proliferation (P < 0.01). Proliferation data were supported by qPCR-data for Ki-67 mRNA. In vitro as well as in vivo, ar-turmerone promoted neuronal differentiation of NSCs. In vivo, after i.c.v. injection of ar-turmerone, proliferating NSCs were mobilized from the subventricular zone (SVZ) and the hippocampus of adult rats, as demonstrated by both [(18)F]FLT-PET and histology (P < 0.05).


CONCLUSIONS
Both in vitro and in vivo data suggest that ar-turmerone induces NSC proliferation. Ar-turmerone thus constitutes a promising candidate to support regeneration in neurologic disease.
Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, Leo-Brandt-Straße 52425, Jülich, Germany. joerg@germanynet.de.|Department of Neurology, University Hospital of Cologne, Cologne, Germany. joerg@germanynet.de.
Joerg
J
Hucklenbroich
Department of Neurology, University Hospital of Cologne, Cologne, Germany. rebecca.klein@uk-koeln.de.|Max Planck Institute for Neurological Research, Cologne, Germany. rebecca.klein@uk-koeln.de.
Rebecca
R
Klein
Max Planck Institute for Neurological Research, Cologne, Germany. bernd.neumaier@nf.mpg.de.
Bernd
B
Neumaier
Max Planck Institute for Neurological Research, Cologne, Germany. rudolf.graf@nf.mpg.de.
Rudolf
R
Graf
Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, Leo-Brandt-Straße 52425, Jülich, Germany. gereon.fink@uk-koeln.de.|Department of Neurology, University Hospital of Cologne, Cologne, Germany. gereon.fink@uk-koeln.de.
Gereon Rudolf
GR
Fink
Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, Leo-Brandt-Straße 52425, Jülich, Germany. michael.schroeter@uk-koeln.de.|Department of Neurology, University Hospital of Cologne, Cologne, Germany. michael.schroeter@uk-koeln.de.|Max Planck Institute for Neurological Research, Cologne, Germany. michael.schroeter@uk-koeln.de.
Michael
M
Schroeter
Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, Leo-Brandt-Straße 52425, Jülich, Germany. adele.rueger@uk-koeln.de.|Department of Neurology, University Hospital of Cologne, Cologne, Germany. adele.rueger@uk-koeln.de.|Max Planck Institute for Neurological Research, Cologne, Germany. adele.rueger@uk-koeln.de.
Maria Adele
MA
Rueger
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D007276:Injections, Intraventricular; D007659:Ketones / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000008:administration & dosage* / Q000494:pharmacology
D007659:Ketones; D018696:Neuroprotective Agents; D012717:Sesquiterpenes; C078098:ar-turmerone