Hematopoietic cell activation in the subventricular zone after Theiler's virus infection

Gwendolyn E Goings,Francis G Szele,Adriana Greisman,Rachel E James,Stephen D Miller,Wendy Smith Begolka,Leanne Kf Abram

doi:10.1186/1742-2094-5-44

Abstract

BackgroundThe periventricular subventricular zone (SVZ) contains stem cells and is an area of active neurogenesis and migration. Since inflammation can reduce neurogenesis, we tested whether Theiler's murine encephalomyelitis virus (TMEV) induces inflammation and reduces neurogenesis in the SVZ.MethodsWe performed immmunohistochemistry for the hematopoietic cell marker CD45 throughout the central nervous system and then examined neuroblasts in the SVZ.ResultsCD45+ activation (inflammation) occurred early in the forebrain and preceded cerebellar and spinal cord inflammation. Inflammation in the brain was regionally stochastic except for the SVZ and surrounding periventricular regions where it was remarkably pronounced and consistent. In preclinical mice, SVZ neuroblasts emigrated into inflamed periventricular regions. The number of proliferating phoshpohistone3+ cells and Doublecortin+ (Dcx) SVZ neuroblasts was overall unaffected during the periods of greatest inflammation. However the number of Dcx+ and polysialylated neural cell adhesion molecule (PSA-NCAM+) SVZ neuroblasts decreased only after periventricular inflammation abated.ConclusionOur results suggest that after TMEV infection, the SVZ may mount an attempt at neuronal repair via emigration, a process dampened by decreases in neuroblast numbers.

Highlights

The periventricular subventricular zone (SVZ) contains stem cells and is an area of active neurogenesis and migration
We show here with an antibody that recognizes all isoforms of CD45, that forebrain CD45+ cell activation precedes spinal cord activation and that the SVZ is the area with the most consistent CD45+ cell activation
Theiler's murine encephalomyelitis virus (TMEV) induces CD45+ cell activation in the forebrain before the spinal cord TMEV was injected in mice into the left cerebellar cortex (Fig. 1A)

Summary

Introduction

The periventricular subventricular zone (SVZ) contains stem cells and is an area of active neurogenesis and migration. The two regions of the brain most intensively scrutinized in recent years for their reparative or cell replacement potential are the subventricular zone (SVZ) which lines the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dentate gyrus [1,2]. Both regions daily (page number not for citation purposes). The SVZ, including human SVZ, contains cells that selfrenew and are multipotential when exposed to appropriate growth factors in vitro; they are stem cells [4] As such, they may provide a source for cell replacement, and many experiments have shown they attempt repair of damaged or diseased tissue [1]. These same migratory routes, fanning out into the forebrain from the SVZ, are followed by SVZ neuronal cells after a variety of injuries and diseases [12,13]

Methods

Results

Conclusion