2010), and other insoluble factors on the plasma membrane (Sudo et al. 1998). Microglia activated by signals from damaged neurons may produce harmful factors that further contribute to neurodegeneration, or by phagocytizing the dying neurons. However, when the neuronal damage is not severe enough to induce neuronal death, microglia may become neuroprotective Inhibitors,research,lifescience,medical and promote neuronal survival by releasing various neuroprotective factors. This duality of function by microglia has long been proposed (Kreutzberg 1996; Streit et al. 1999; Cullheim and Thams 2007), and agents

that change the FTY720 in vivo microglial phenotype from destructive to protective have been sought for a long time as treatments for neurological disorders. This cytokine mixture may have this microglial phenotype-changing

activity. The beneficial effect of this cytokine mixture may also be related to its ability to increase the expression of Bcl-xL Inhibitors,research,lifescience,medical in neurons. This effect may promote the survival of damaged neurons, activate the neuroprotective actions of surrounding microglia, and further bolster neuronal survival. Expression of NG2 by microglia may be another hallmark of their activation (Yokoyama et al. 2006; Kitamura et al. 2010; Zhu et al. 2010). Although NG2+ microglia have been reported to express a neuroprotective factor, GDNF (Kitamura et al. 2010), it appears that in the present scenario this neuroprotective factor did not contribute Inhibitors,research,lifescience,medical to neuronal survival in the 6-OHDA-induced Parkinsonism model. This is because NG2+ microglia were present following 6-OHDA treatment without

and with cytokine treatment. 6-OHDA-induced neurotoxicity has been attributed to oxidative stress (Glinka et al. 1997). Inhibitors,research,lifescience,medical Astrocytes have strong antioxidant properties (Tanaka et al. 1999; Inhibitors,research,lifescience,medical Miyazaki et al. 2011), and activated astrocytes are known to prevent DArgic neurodegeneration (Asanuma et al. 2010; Choudhury et al. 2011). Activated astrocytes were also evident in this study and the expression of mRNAs encoding Cu/Zn SOD and metallothionein 2, both of which play critical roles in suppressing oxidative stress, were upregulated in parallel with increased GFAP expression in the SNpc of the saline group. However, the activation of astrocytes and the upregulation of antioxidant factors did not lead to improved survival of neurons. Furthermore, when neurodegeneration was suppressed Parvulin with the cytokine mixture, both astrocytic activation and the expression of antioxidative factors were also suppressed, suggesting that astrocytes and the antioxidative factors do not contribute to DArgic neuronal survival in the presence of the cytokines. On the other hand, NG2 glia may contribute to the survival of DArgic neurons. NG2 glia are abundantly distributed throughout the brain and the spinal cord, representing 5–15% of nonneuronal cells (Staugaitis and Trapp 2009; Trotter et al. 2010). Some of these cells are also oligodendrocyte progenitor cells.