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 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.
Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, Largo Marquês de Pombal, 3004-504 Coimbra, Portugal. libernardino@gmail.com
Liliana
L
Bernardino
Maria Francisca
MF
Eiriz
Tiago
T
Santos
Sara
S
Xapelli
Sofia
S
Grade
Alexandra Isabel
AI
Rosa
Luísa
L
Cortes
Raquel
R
Ferreira
José
J
Bragança
Fabienne
F
Agasse
Lino
L
Ferreira
João O
JO
Malva
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006632:Histamine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry; D020547:Lateral Ventricles / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006632:Histamine