title: Galanin promotes neuronal differentiation in murine subventricular zone cell cultures.
abstract: 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.
authors: Center for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês de Pombal, Coimbra, Portugal.
authors: Fabienne
authors: F
authors: Agasse
authors: Sara
authors: S
authors: Xapelli
authors: Valérie
authors: V
authors: Coronas
authors: Søren H
authors: SH
authors: Christiansen
authors: Alexandra I
authors: AI
authors: Rosa
authors: Laura
authors: L
authors: Sardá-Arroyo
authors: Tiago
authors: T
authors: Santos
authors: Raquel
authors: R
authors: Ferreira
authors: Clarissa
authors: C
authors: Schitine
authors: Thomas
authors: T
authors: Harnois
authors: Nicolas
authors: N
authors: Bourmeyster
authors: José
authors: J
authors: Bragança
authors: Liliana
authors: L
authors: Bernardino
authors: João O
authors: JO
authors: Malva
authors: David P D
authors: DP
authors: Woldbye
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002552:Cerebral Ventricles / Q000166:cytology / Q000187:drug effects; D004268:DNA-Binding Proteins; D019004:Galanin / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis; D010446:Peptide Fragments / Q000494:pharmacology; D044091:Receptor, Galanin, Type 1 / Q000378:metabolism*; D044092:Receptor, Galanin, Type 2 / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000096:biosynthesis
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D019004:Galanin; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D044091:Receptor, Galanin, Type 1; D044092:Receptor, Galanin, Type 2; D014446:Tyrosine 3-Monooxygenase; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C079240:Mtap2 protein, mouse; C492380:NeuN protein, mouse; C434734:galanin (2-11)-amide; C493406:vesicular GABA transporter; C486336:Neurog1 protein, mouse