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

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.

Mast cells increase adult neural precursor proliferation and differentiation but this potential is not realized in vivo under physiological conditions

“…This result is not consistent with previously reported effects of histamine on neonatal SVZ stem/progenitor cells where a strong pro-neurogenic effect of histamine on neonatal SVZ and embryonic cortical cell cultures was observed, without changes in proliferation 34 , 35 . Another report has demonstrated that chronic histamine administration in the adult SVZ in vivo does not induce an overall increase in cell proliferation but instead may trigger neuronal commitment of SVZ cells, and identified histamine as a crucial modulator of neuronal differentiation in the SVZ-OB axis 36 . Nevertheless, in published in vitro studies 500 μM was the highest histamine concentration tested, possibly indicating that elevated concentrations of histamine (1 mM) may be needed to activate SVZ cell proliferation.…”

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

“…The experiments were performed in three independent cultures, unless stated otherwise, and for each experimental condition at least 2 coverslips were assayed per culture. the SVZ, OB (granule (GCL) and glomerular (GL) layers) and striatum of at least 3 animals, as described previously by us [8]. Figure 1D arrowhead).…”

“…microRNAs) [6][7][8][9] regulate the neurogenic niche. MicroRNAs (miR) are able to regulate hundreds of genes [10] at the posttranscriptional level by inhibiting mRNA translation or inducing mRNA degradation [11].…”

Adult neurogenesis 20 years later: physiological function vs. brain repair

“…The article by Turnley et al addresses this lack of survival and integration as one of the major bottlenecks that inhibits effective neuronal replacement. They analyze factors that enhance newborn neuron survival and integration under normal physiological conditions, including neurotransmitters, cytoskeletal rearrangements, neurotrophins, and other modulators of neural plasticity (see also Eiriz et al, 2014 ). Other crucial and unresolved questions were addressed by our Perspective article (Peretto and Bonfanti, 2014 ): comparative analyses have not yet elucidated to which extent brain regenerative capability is a byproduct of evolution and to which extent the knowledge of mechanisms in physiological plasticity can implement brain repair.…”