We assume that Gpnmb produced by infiltrating macrophages may counteract or decrease the actions of these proinflammatory cytokines. Recently, a genome-wide association study identified the human Gpnmb gene on chromosome 7p15 as a risk locus for Parkinson’s disease (International Parkinson’s Disease Genomics Consortium (IPDGC) and Wellcome Trust Case Control Consortium 2 (WTTCCC2) 2011). Considering the present observation that Gpnmb-IR is detectable in ED1- or OX42-positive cells in the striatum (Fig. S3), it is tempting to postulate that Gpnmb may exert an anti-inflammatory effect during the degeneration of nigrostriatal neurons. In addition to macrophage/microglia these lineage cells,

we detected Gpnmb-IR in ependymal, Bergmann glial, and NeuN-positive Inhibitors,research,lifescience,medical neuronal cells. Ependymal cells, like astrocytes, can be generated from radial glia (Spassky et al. 2005; Wang and Bordey 2008) and express GFAP (Doetsch et al. 1997; Liu et al. 2006; Wang Inhibitors,research,lifescience,medical and Bordey 2008). Bergmann glial cells are radial glia that persist in the adult cerebellum without differentiating into mature astrocytes (Kriegstein and Götz 2003; Rakic 2003; Wang and Bordey 2008) and regarded as specialized astrocytes (Rakic 2003). Although these Inhibitors,research,lifescience,medical GFAP-positive cells are originated from radial glia, Gpnmb-IR was detected only in ependymal and Bergmann glial cells, but not in the majority of astrocytes. One possible

explanation for this difference is that Gpnmb expression in ependymal and Bergmann glial cells may take place after commitment to terminal differentiation. Although the nature and ontogenic origin of Gpnmb and NeuN double-positive cells are currently unclear, Gpnmb-IR in hippocampal granular cell Inhibitors,research,lifescience,medical neurons could

be explained as a remnant of radial glia, from which these neurons originated (Kriegstein and Götz 2003). Elucidation of the role of Gpnmb Inhibitors,research,lifescience,medical in these cell types requires more detailed characterization during development. In conclusion, the present results indicate that Gpnmb was expressed in microglia/macrophage and radial glial lineage cells in non-tumorous neural tissues. It is therefore conceivable that Gpnmb-targeted therapies may have detrimental effects Batimastat on these cell types. More importantly, our findings raise the possibility that Gpnmb may serve as a novel regulator of immune/inflammatory responses in CNS. Future studies are needed to clarify the role of Gpnmb in immune/inflammatory responses underlying traumatic nerve injury and neurodegenerative diseases, such as multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease. Acknowledgments We thank O. Takahashi for high-magnification fluorescence microscopy. This work was supported in part by grants from the Ministry of Education, Culture, Science, Sports and Technology of Japan. Supporting Information Additional Supporting Information may be found in the online version of this article: Figure. S1. Characterization of Gpnmb-IR cells in cortical layer VI with multiple markers. Click here to view.(4.