Plasminogen activator inhibitor-1 promotes synaptogenesis and protects against aβ(1-42)-induced neurotoxicity in primary cultured hippocampal neurons

• Published in: International journal of neuroscience 2013-01, Vol.123 (1), p.42
• Main Authors: Cho, Harim, Joo, Yuyoung, Kim, Seonghan, Woo, Ran-Sook, Lee, Sang Hyung, Kim, Hye-Sun
• Format: Article
• Language: English
• Subjects: Amyloid beta-Peptides - toxicity; Analysis of Variance; Animals; Cells, Cultured; Disks Large Homolog 4 Protein; Fetus; Hippocampus - cytology; Humans; Intracellular Signaling Peptides and Proteins - metabolism; L-Lactate Dehydrogenase; Membrane Proteins - metabolism; Neural Cell Adhesion Molecule L1 - metabolism; Neurons - drug effects; Neurons - enzymology; Peptide Fragments - toxicity; Plasminogen Activator Inhibitor 1 - pharmacology; Rats; Sialic Acids - metabolism; Synapses - drug effects; Synaptophysin - metabolism; Up-Regulation - drug effects
• ISSN: 1563-5279
• DOI: 10.3109/00207454.2012.724127

Plasminogen activator inhibitor-1 (PAI-1) is a soluble factor that is released from astrocytes, the most abundant type of glial cell in the brain. PAI-1 was initially identified as inhibiting two types of plasminogen activators, that is, tissue-type plasminogen and urokinase activators that are known to lead to the proteolytic degradation of the extracellular matrix. Recently, PAI-1 was reported to mediate the neuroprotective activity of transforming growth factor-β1 against N-methyl-D-aspartate receptor-mediated excitotoxicity and to be involved in angiogenesis following ischemic stroke, independently of the effects via the inhibition of tissue-type plasminogen and urokinase-type plasminogen activators. In this study, we examined whether PAI-1 influences synaptogenesis and neurotoxicity induced by amyloid beta peptide(1-42) (Aß(1-42)) in rat primary hippocampal neurons. Using immunostaining, treatment with PAI-1 for 24 h was found to significantly upregulate synaptophysin, postsynaptic density-95, and the polysialylated form of neural cell adhesion molecule, compared to treatment with vehicle alone. In addition, PAI-1 has neuroprotective effects against Aβ(1-42)-induced cytotoxicity in rat primary cultured hippocampal neurons. Taken together, our results suggest that PAI-1 has therapeutic potential in Alzheimer's disease by promoting synaptogenesis and by demonstrating neuroprotective effects against Aβ(1-42)-oligomer-induced neurotoxicity in rat primary cultured hippocampal neurons.