Neuropeptide Y Y1 receptor is neuroprotective and modulates microglia reactivity in the rat retina

Abstract

AbstractPurpose Neuropeptide Y (NPY) is neuroprotective and can regulate inflammation. In the retina, microglia (MG) activation has been implicated in the pathogenesis of several diseases. We investigated whether NPY, particularly through Y1 receptor (Y1r) activation, is neuroprotective and modulates pro‐inflammatory responses in the retina.Methods Immunocytochemistry, RT‐PCR, TUNEL and ELISA were used.Results NPY and NPY Y1, Y2 and Y5 receptors were detected in retinal ganglion cells (RGC) and MG. The increase in TUNEL‐positive cells in the ganglion cell layer induced by exposure of retinal explants to NMDA was inhibited by Y1r activation. Exposure to LPS activated retinal MG, and NPY prevented MG morphological changes via Y1r. NPY or [Leu31, Pro34]‐NPY (LP‐NPY; Y1r/Y5r agonist) inhibited the increase in iNOS immunoreactivity triggered by LPS, and BIBP 3226 (Y1r antagonist) abolished the effect of LP‐NPY. LPS also increased the concentration of TNF‐alpha, IL‐1beta and IL‐6. NPY inhibited the increase in IL‐1beta and IL‐6, but not TNF‐alpha. Moreover, LP‐NPY inhibited the increase in TNF‐alpha, IL‐1beta and IL‐6, and BIBP 3226 abrogated the effect of LP‐NPY.Conclusion In conclusion, RGC and MG express NPY and NPY Y1, Y2 and Y5 receptors. The activation of Y1r can exert neuroprotective effects in RGC and induce anti‐inflammatory effects in the retina, inhibiting MG activation. Support: FCT (PTDC/SAU‐NEU/099075/2008, PTDC/NEU‐OSD/1113/2012, PEst‐C/SAU/UI3282/2011‐2012, PEst‐C/SAU/LA0001/2011‐2012, SFRH/BPD/69123/2010, SFRH/BD/44817/2008), Portugal, and COMPETE‐FEDER.