As shown in the present study, NG2 glia appeared to increase in number and to attach intimately to damaged DArgic neurons in the SNpc in the cytokine group. Elevation of PCNA-mRNA may be related to the proliferation of NG2 glia. In contrast to astrocytes, the increase in the occupying area

by NG2 glia and their attachment to DArgic neurons were prominent in the cytokine group, and therefore, it is possible that NG2 glia elicit Inhibitors,research,lifescience,medical neuroprotective effects under the influence of the cytokine mixture. However, NG2 glia did not express receptors for GM-CSF, and IL-3. NG2 glia may respond to IGF-1 and HGF released by microglia. IGF-1 has been shown to be crucial for the survival of NG2 glial cells (Sundberg et al. 2010). NG2 glia express c-Met/HGF receptor, and HGF promotes NG2 glial proliferation (Ohya et al. 2007). In the present study, the cytokine mixture was found to upregulate expressions of IGF-1 and HGF in cultured Inhibitors,research,lifescience,medical microglia and in microglia in the ventral

midbrain. Therefore, the cytokine mixture may stimulate NG2 glial survival and proliferation through IGF-1 and HGF, which is released by microglial cells in the SNpc of the cytokine-treated Inhibitors,research,lifescience,medical rats. In conclusion, this study demonstrated the neuroprotective effects of a cytokine mixture containing GM-CSF and IL-3. A summary of our findings is shown in Figure 9. We propose that 6-OHDA administration into the striatum causes DArgic neurodegeneration in the SNpc and accompanying microglial activation (Fig. 9). The activated microglia produce proinflammatory cytokines that cause further chronic neurodegeneration. This neurodegeneration may also cause further activation of microglia, which in this scenario is not neuroprotective. Thus, a vicious cycle of neuronal degeneration occurs (Levesque Inhibitors,research,lifescience,medical et al. 2010). On the other hand, when the cytokine mixture is injected, DArgic neurons increase Bcl-xL expression, and thus, these neurons avoid degeneration in the face of 6-OHDA FHPI molecular weight toxicity. In this scenario, the microglia become activated and display an activated morphology, similar to that in the saline

Inhibitors,research,lifescience,medical group, but in this case they suppress proinflammatory cytokine expression. The microglia in the cytokine mixture-treated group have enhanced expression of the neuroprotective factors IGF-1 and HGF. IGF-1 and HGF enhances not only the Sclareol viability of neurons but also the survival and production of NG2 glia, which can contribute to neuronal survival. Therefore, it is proposed that this cytokine mixture has neuroprotective properties and could help in the treatment of PD. Figure 9 A summarized scheme based on the present data. 6-OHDA-induced DArgic neurodegeneration accompanies microglial activation. Without the cytokine mixture injection, activated microglia (MG) release the proinflammatory cytokine IL-1β and TNFα, … Acknowledgments We are grateful to Staffs in Animal Center for their gentle care to animals and to M.