Plasminogen Activator Inhibitor-1의 해마 시냅스 기능 및 Aβ oligomers에 의한 신경세포 손상에 대한 보호 효과에 관한 연구

Abstract

Neuroprotection is considered to be necessary for preventing neurodegeneration. Recently, it has been suggested that glia suppress the upregulation of proinflammatory cytokines and attenuate neurodegeneration. Plasminogen activator inhibitor-1 (PAI-1) is a soluble factor that is released from astrocytes. PAI-1 was previously reported to mediate the neuroprotective activity of TGF-beta 1 against N-methyl-D-aspartate receptor-mediated excitotoxicity. However, it is unclear whether PAI-1 influences synaptogenesis and synaptic plasticity; it is also unclear whether PAI-1 exerts neuroprotective effects against neuronal death induced by Aβ1-42 oligomers. First, using immunocytochemical technique, we examined the expression profile of synaptophysin and PSD-95, markers for functional synapses. The expression of polysialic acid-neural cell adhesion molecule (PSA-NCAM) was also examined with immunocytochemistry to explore the effect of PAI-1 on synaptic plasticity. We found that PAI-1 treatment increased protein levels of synaptophysin, PSD-95, and PSA-NCAM in primary cultured hippocampal neurons. In addition, we found that PAI-1 protected primary hippocampal neurons from neurotoxicity induced by Aβ1-42 oligomers. Taken together, our results demonstrate that PAI-1 promoted synaptogenesis and exerts neuroprotective effects against Aβ1-42 oligomers-induced neurotoxicity in rat primary hippocampal neurons and slices.