Tissue-Specific Stem Cells

Histamine Stimulates Neurogenesis in the Rodent Subventricular Zone†

  1. Liliana Bernardino1,2,‡,§,*,
  2. Maria Francisca Eiriz1,§,
  3. Tiago Santos1,
  4. Sara Xapelli1,
  5. Sofia Grade1,
  6. Alexandra Isabel Rosa1,
  7. Luísa Cortes1,
  8. Raquel Ferreira1,
  9. José Bragança3,
  10. Fabienne Agasse1,
  11. Lino Silva Ferreira1,
  12. João O. Malva1,‡

DOI: 10.1002/stem.1042

Additional Information

Author Information

  1. 1

    Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, Largo Marquês de Pombal, 3004-504 Coimbra, Portugal

  2. 2

    Health Sciences Research Center, University of Beira Interior, 6200-506 Covilhã, Portugal

  3. 3

    Institute for Biotechnology and Bioengineering, Centre for Molecular and Structural Biomedicine, University of Algarve, 8005-139 Faro, Portugal

  1. ‡

    phone: +351 239 820 190, fax: +351 239 822 776

  2. §

    Liliana Bernardino and Maria Francisca Eiriz contributed equally to the manuscript;

*Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, Largo Marquês de Pombal, 3004-504 Coimbra, Portugal

  1. †

    Author contributions: L.B.: Conception and design; Financial support; Administrative support; Provision of study material; Collection and/or assembly of data; Data analysis and interpretation; Manuscript writing; Final approval of manuscript.; M.F.E.: Conception and design; Provision of study material; Collection and/or assembly of data; Data analysis and interpretation; Manuscript writing; Final approval of manuscript.; T.S.: Provision of study material; Collection and/or assembly of data; Data analysis and interpretation.; S.X.: Provision of study material; Collection and/or assembly of data.; S.G.: Provision of study material; Collection and/or assembly of data.; A.I.R.: Provision of study material; Collection and/or assembly of data.; L.C.: Provision of study material; Collection and/or assembly of data.; R.F.: Provision of study material; Collection and/or assembly of data.; J.B.: Provision of study material; Collection and/or assembly of data.; F.A.: Conception and design; Financial support; Administrative support; Provision of study material; Collection and/or assembly of data; Data analysis and interpretation.; L.F.: Conception and design; Financial support; Provision of study material; Collection and/or assembly of data; Data analysis and interpretation.; J.O.M.: Conception and design; Financial support; Data analysis and interpretation; Manuscript writing; Final approval of manuscript.

Publication History

  1. Accepted manuscript online: 20 JAN 2012 11:01AM EST
  2. Manuscript Accepted: 29 DEC 2011
  3. Manuscript Received: 28 JUL 2011

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Keywords:

  • Subventricular Zone;
  • Histamine;
  • Biocompatible microparticles;
  • Neuronal differentiation

Abstract

Neural stem/progenitor cells present in the subventricular zone (SVZ) are a potencial 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) (PLGA) 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.

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