Over-Expression of Meteorin Drives Gliogenesis Following Striatal Injury.

Jordan L Wright,Charlotte M Ermine,Jesper R Jørgensen,Lachlan H Thompson,Clare L Parish

doi:10.3389/fncel.2016.00177

Abstract

A number of studies have shown that damage to brain structures adjacent to neurogenic regions can result in migration of new neurons from neurogenic zones into the damaged tissue. The number of differentiated neurons that survive is low, however, and this has led to the idea that the introduction of extrinsic signaling factors, particularly neurotrophic proteins, may augment the neurogenic response to a level that would be therapeutically relevant. Here we report on the impact of the relatively newly described neurotrophic factor, Meteorin, when over-expressed in the striatum following excitotoxic injury. Birth-dating studies using bromo-deoxy-uridine (BrdU) showed that Meteorin did not enhance injury-induced striatal neurogenesis but significantly increased the proportion of new cells with astroglial and oligodendroglial features. As a basis for comparison we found under the same conditions, glial derived neurotrophic factor significantly enhanced neurogenesis but did not effect gliogenesis. The results highlight the specificity of action of different neurotrophic factors in modulating the proliferative response to injury. Meteorin may be an interesting candidate in pathological settings involving damage to white matter, for example after stroke or neonatal brain injury.

Highlights

Meteorin is a member of a newly described family of secreted proteins that includes the related protein, Meteorin-like
Compared to the lentiviral vectors carrying either GFP (lvGFP) control group, no significant difference was observed in the percentage of Iba1+/BrdU+ cells in the lvMeteorin groups (49.3 ± 8.2% of BrdU+ cells; p = 0.27) and the lvGDNF group (31.1 ± 5% of BrdU+ cells; p = 0.72; one-way ANOVA, Bonferroni post hoc) – Figure 4G indicating that these factors did not influence microglia proliferation post-striatal injury. These results show that lentiviral delivery of Meteorin to the damaged striatum leads to robust over-expression of the diffusible protein resulting in increased gliogenesis but not neurogenesis in response to striatal injury
This has led to the idea that augmentation of this neurogenic response might lead to regenerative therapies for brain repair

Summary

Introduction

Meteorin is a member of a newly described family of secreted proteins that includes the related protein, Meteorin-like It is highly expressed in the mammalian brain, throughout midto late-development and is maintained at lower levels in the post-natal brain (Jorgensen et al, 2009). Meteorin protein is most conspicuously expressed by Bergmann glia in the cerebellum, and more diffusely at lower levels in glia cells throughout the brain. It was first characterized in vitro for its ability to promote astrocyte differentiation and axon growth in neurosphere cultures and dorsal root ganglion explants, respectively, (Nishino et al, 2004). Studies have begun to investigate the possibility that, in addition to neuroprotection

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Conclusion