Histamine Stimulates Neurogenesis in the Rodent Subventricular Zone

Neural stem/progenitor cells present in the subventricular zone (SVZ) are a potential source of repairing cells after injury. Therefore, the identification of novel players that modulate neural stem cells differentiation can have a huge impact in stem cell‐based therapies. Herein, we describe a uniq...

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Published in:Stem cells (Dayton, Ohio) Ohio), 2012-04, Vol.30 (4), p.773-784
Main Authors: Bernardino, Liliana, Eiriz, Maria Francisca, Santos, Tiago, Xapelli, Sara, Grade, Sofia, Rosa, Alexandra Isabel, Cortes, Luísa, Ferreira, Raquel, Bragança, José, Agasse, Fabienne, Ferreira, Lino, Malva, João O.
Format: Article
Language:English
Subjects:
Animals
Biocompatible microparticles
Cell Culture Techniques
Cell Differentiation - drug effects
Cell Growth Processes - drug effects
Cell Survival - drug effects
Cells, Cultured
Histamine
Histamine - administration & dosage
Histamine - chemistry
Histamine - pharmacology
Lactic Acid - administration & dosage
Lactic Acid - chemistry
Lateral Ventricles - cytology
Lateral Ventricles - drug effects
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neural Stem Cells - cytology
Neural Stem Cells - drug effects
Neurogenesis - drug effects
Neuronal differentiation
Polyglycolic Acid - administration & dosage
Polyglycolic Acid - chemistry
Subventricular zone
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Summary:Neural stem/progenitor cells present in the subventricular zone (SVZ) are a potential source of repairing cells after injury. Therefore, the identification of novel players that modulate neural stem cells differentiation can have a huge impact in stem cell‐based therapies. Herein, we describe a unique role of histamine in inducing functional neuronal differentiation from cultured mouse SVZ stem/progenitor cells. This proneurogenic effect depends on histamine 1 receptor activation and involves epigenetic modifications and increased expression of Mash1, Dlx2, and Ngn1 genes. Biocompatible poly (lactic‐co‐glycolic acid) microparticles, engineered to release histamine in a controlled and prolonged manner, also triggered robust neuronal differentiation in vitro. Preconditioning with histamine‐loaded microparticles facilitated neuronal differentiation of SVZ‐GFP cells grafted in hippocampal slices and in in vivo rodent brain. We propose that neuronal commitment triggered by histamine per se or released from biomaterial‐derived vehicles may represent a new tool for brain repair strategies. STEM CELLS 2012; 30:773–784
ISSN:1066-5099
1549-4918
DOI:10.1002/stem.1042