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Pleiotrophin (PTN) is a secreted heparin-binding cytokine that signals diverse functions, including lineage-specific differentiation of glial progenitor cells, axonal outgrowth and angiogenesis. Neurotoxicity mediated by glutamate receptor is thought to play a role in various neurodegenerative disorders. In the present study, we examined the effect of PTN on the neuronal viability of hippocampal neurons in vitro by using the immunostaining of MAP2 and permeability of propidium iodide. PTN significantly prevented glutamate-induced neurotoxicity when hippocampal neurons were treated with PTN after the glutamate stimulation. PTN significantly promoted glutamate-induced neurotoxicity, when cells were incubated with PTN before and after the glutamate stimulation. Thus, the effect of PTN on the neuronal viability of hippocampal neurons largely depends on the timing of the treatment of PTN. The treatment of PTN promoted dendrite-specific expression of MAP2, indicating that PTN stabilizes microtubule system at dendrites. The data suggest that PTN may be relevant to be concerned with glutamate-induced neurotoxicity of hippocampal neurons.

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