Abstract

The subventricular zone (SVZ) contains neural stem cells (NSCs) that generate new neurons throughout life. Many brain diseases stimulate NSCs proliferation, neuronal differentiation and homing of these newborns cells into damaged regions. However, complete cell replacement has never been fully achieved. Hence, the identification of proneurogenic factors crucial for stem cell-based therapies will have an impact in brain repair. Histamine, a neurotransmitter and immune mediator, has been recently described to modulate proliferation and commitment of NSCs. Histamine levels are increased in the brain parenchyma and at the cerebrospinal fluid (CSF) upon inflammation and brain injury, thus being able to modulate neurogenesis. Herein, we add new data showing that in vivo administration of histamine in the lateral ventricles has a potent proneurogenic effect, increasing the production of new neuroblasts in the SVZ that ultimately reach the olfactory bulb (OB). This report emphasizes the multidimensional effects of histamine in the modulation of NSCs dynamics and sheds light into the promising therapeutic role of histamine for brain regenerative medicine.

Highlights

  • Brain diseases represent a very demanding worldwide health challenge

  • We comment on recent data supporting the role of histamine as a robust proneurogenic factor in vivo and we discuss the profits vs. challenges for its usage in stem cell-based brain repair therapies

  • We found that subventricular zone (SVZ) neural stem cells (NSCs) labelled with BrdU have differentiated into migrating neuroblasts that reached the olfactory bulb (OB) in control and more densely in histamine treated animals (Figure S1B, and Figure 2)

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Summary

Introduction

Brain diseases represent a very demanding worldwide health challenge. no effective cure exists for the majority of these disorders. We found that the intracerebroventricular (i.c.v.) infusion of histamine in the lateral ventricles for 21 days induced a trend increase in the number of BrdU retaining cells (BrdU+DCX−) at the SVZ (Control: 25.8 ± 2.7; Histamine: 34.4 ± 4.7; statistically not-significant).

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