Histamine Stimulates Neurogenesis in the Rodent Subventricular Zone

Author:

Bernardino Liliana12,Eiriz Maria Francisca1,Santos Tiago1,Xapelli Sara1,Grade Sofia1,Rosa Alexandra Isabel1,Cortes Luísa1,Ferreira Raquel1,Bragança José3,Agasse Fabienne1,Ferreira Lino1,Malva João O.14

Affiliation:

1. Center for Neuroscience and Cell Biology, Portugal

2. Health Sciences Research Center, University of Beira Interior, Covilhã, Portugal

3. Institute for Biotechnology and Bioengineering, Centre for Molecular and Structural Biomedicine, University of Algarve, Faro, Portugal

4. Faculty of Medicine, University of Coimbra, Largo Marquês de Pombal, Coimbra, Portugal

Abstract

Abstract 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. Disclosure of potential conflicts of interest is found at the end of this article.

Funder

Fundação para a Ciência e a Tecnologia-Portugal

Fundação Calouste Gulbenkian

MIT-Portugal Program (focus in Bioengineering

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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