Histamine Stimulates Neurogenesis in the Rodent Subventricular Zone

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.

MicroRNA-124 loaded nanoparticles enhance brain repair in Parkinson's disease

“…Viral vectors have a high capacity to deliver miR, however safety issues such as immunogenicity and the risk of triggering oncogenic transformation limits its translation potential [23]. Non-viral vectors such as polymeric nanoparticles (NPs), which avoid these safety issues, have been used by us and others to efficiently deliver proneurogenic molecules, including miR, into cells [7,[23][24][25]. As so, we hypothesized that the use of polymeric NPs to deliver miR-124 could promote neurogenesis of SVZ NSCs both in vitro and in vivo and ultimately promote brain repair.…”

New insights into the role of histamine in subventricular zone-olfactory bulb neurogenesis

“…Recently, it was shown that histamine has a strong proneurogenic effect in neonatal SVZ (Bernardino et al, 2012) and in embryonic cortical cell cultures (Molina-Hernández and Velasco, 2008; Rodríguez-Martínez et al, 2012; Molina-Hernández et al, 2013) via H1R activation. Histamine may trigger increased transcription of FGFR1 and increased cell proliferation culminating in the differentiation of FOXP2 neuronal cells both in vitro and in vivo (Rodríguez-Martínez et al, 2012; Molina-Hernández et al, 2013) (Figure S1A).…”

Neuronal histamine and cognitive symptoms in Alzheimer's disease

“…However, the clinical trials performed so far with the histamine-related drugs that are at hand suggest that these compounds have either no effect or only minor beneficial effects on cognitive performance in patients suffering from Alzheimer disease (Grove et al, 2014;Nathan et al, 2013). Recent findings have implicated the neuronal histaminergic system in neurogenesis in the hippocampus and sub-ventricular zone/olfactory bulb (Ambree et al, 2014;Bernardino et al, 2012). As a perspective for future studies, it remains to be determined whether novel histamine-related drugs or "cocktail therapies" that include histamine-related agents could stimulate hippocampal neurogenesis in addition to an amelioration of cognitive deficits (including episodic-like memory) in animal models of Alzheimer's disease.…”

“…It has been shown that histamine itself can stimulate neurogenesis in the rodent subventricular zoneolfactory bulb (that contains neural stem cells and is a source of newly generated neurons across adulthood) in vitro and vivo (Bernardino et al, 2012(Bernardino et al, , 2010Eiriz et al, 2014). Furthermore, it has been reported that histamine applied to a cell culture preparation that contained neuronal precursor cells increased the number of FOXP2-positive neurons (Molina-Hernandez et al, 2013).…”