Galanin promotes neuronal differentiation in murine subventricular zone cell cultures
Autor: | David P.D. Woldbye, Tiago Santos, Raquel Ferreira, Thomas Harnois, Liliana Bernardino, Laura Sardà-Arroyo, Nicolas Bourmeyster, Fabienne Agasse, José Bragança, Alexandra Isabel Rosa, João O. Malva, Søren H. Christiansen, Clarissa S. Schitine, Sara Xapelli, Valérie Coronas |
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Rok vydání: | 2013 |
Předmět: |
medicine.medical_specialty
Tyrosine 3-Monooxygenase Vesicular Inhibitory Amino Acid Transport Proteins animal diseases Neurogenesis Neuronal differentiation Cell Culture Techniques Subventricular zone Galanin Nerve Tissue Proteins Brain damage Biology Cerebral Ventricles Mice Neural Stem Cells Cell Movement Internal medicine medicine Basic Helix-Loop-Helix Transcription Factors Animals Receptor Cells Cultured Cell Proliferation Neurons Cell Death Nuclear Proteins Cell Differentiation Cell Biology Hematology Cell movement Neural stem cell Peptide Fragments Receptor Galanin Type 1 Cell biology Receptor Galanin Type 2 DNA-Binding Proteins Mice Inbred C57BL Endocrinology medicine.anatomical_structure nervous system Cell culture medicine.symptom Microtubule-Associated Proteins Developmental Biology |
Zdroj: | Stem cells and development. 22(11) |
ISSN: | 1557-8534 |
Popis: | Neural stem cells of the subventricular zone (SVZ) represent a potentially important source of surrogate cells for the treatment of brain damage. Proper use of these cells for neuronal replacement depends on the ability to drive neuronal differentiation. Several neuromodulators stimulate neurogenesis. Here we examined the effects of the neuropeptide galanin, on neuronal differentiation in murine SVZ cultures. SVZ neurospheres obtained from early postnatal mice were treated with 10 nM to 2 μM galanin. Galanin promoted neuronal differentiation, increasing numbers of NeuN-, vesicular GABA transporter- and tyrosine hydroxylase-expressing neurons. In contrast, galanin neither affected cell proliferation assessed by BrdU incorporation nor cell death evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Neuronal differentiation was further confirmed at the functional level by measuring [Ca(2+)]i variations in single SVZ cells after KCl and histamine stimulations to distinguish neurons from immature cells. Galanin treatment increased the numbers of neuronal-like responding cells compared to immature cells. Using selective agonists (M617, AR-M1896) and antagonists (galantide, M871) for galanin receptors 1 and 2, we showed that both galanin receptors mediated neuronal differentiation. Early proneuronal effects of galanin included positive regulation of the transcription factor neurogenin-1 (Ngn1). In addition, galanin promoted axonogenesis and dendritogenesis, increasing both the length of phosphorylated stress-activated protein kinase- and Tau-positive axons and the numbers of microtubule associated protein-2 (MAP-2)-labelled dendrites. Moreover, galanin inhibited SVZ cell migration in the transwell assay. Our results show a proneurogenic effect of galanin and open new perspectives for future applications in stem cell-based therapies for neuronal replacement. |
Databáze: | OpenAIRE |
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