IL-10 regulates adult neurogenesis by modulating ERK and STAT3 activity.

Leticia Pereira,Chris Van Den Haute,Esther Pozas,Miriam Font-Nieves,Veerle Baekelandt,Anna M Planas

doi:10.3389/fncel.2015.00057

Abstract

The adult subventricular zone (SVZ) contains Nestin+ progenitors that differentiate mainly into neuroblasts. Our previous data showed that interleukin-10 (IL-10) regulates SVZ adult neurogenesis by up-regulating the expression of pro-neural genes and modulating cell cycle exit. Here we addressed the specific mechanism through which IL-10 carries out its signaling on SVZ progenitors. We found that, in vitro and in vivo, IL-10 targets Nestin+ progenitors and activates the phosphorylation of ERK and STAT3. The action of IL-10 on Nestin+ progenitors is reversed by treatment with a MEK/ERK inhibitor, thus restoring neurogenesis to normal levels. Silencing STAT3 expression by lentiviral vectors also impaired neurogenesis by blocking the effects of IL-10. Our findings unveil ERK and STAT3 as effectors of IL-10 in adult SVZ neurogenesis.

Highlights

Postnatal neurogenesis takes place in restricted regions or niches in the adult brain
Double immunofluorescence analysis demonstrated that low levels of pSTAT3ser727 were constitutively present in the nuclei of subventricular zone (SVZ) neural cells and they did not change in the presence of the vehicle
In a previous study we described that IL-10 modulates the undifferentiated state of SVZ neural progenitors by up-regulating neural markers, such as Nestin, Musashi, and Notch intracellular domain (NICD), while it decreases the expression of NUMB, a protein involved in neuronal differentiation (Perez-Asensio et al, 2013)

Summary

Introduction

Postnatal neurogenesis takes place in restricted regions or niches in the adult brain. The SVZ lining the LVs is one of the main neurogenenic niches in the adult brain. The relationships between the different cell types, the cerebrospinal fluid (CSF), and the vasculature modulate the molecular signals that regulate self-renewal, proliferation, the identity of VZ-SVZ-derived progeny, the integration of some intrinsic mechanisms (Guillemot, 2007; Lim et al, 2009; Ihrie et al, 2011)

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