Pigment epithelium-derived factor up-regulation induced by memantine, an N-methyl-D-aspartate receptor antagonist, is involved in increased proliferation of hippocampal progenitor cells

Neuroscience
Takashi NambaShigeo Uchino

Abstract

Memantine is classified as an NMDA receptor antagonist. We recently reported that memantine promoted the proliferation of neural progenitor cells and the production of mature granule neurons in the adult hippocampus. However, the molecular mechanism responsible for the memantine-induced promotion of cellular proliferation remains unknown. In this study we searched for a factor that mediates memantine-induced cellular proliferation, and found that pigment epithelium-derived factor (PEDF), a broad-acting neurotrophic factor, is up-regulated in the dentate gyrus of adult mice after the injection of memantine. PEDF mRNA expression increased significantly by 3.5-fold at 1 day after the injection of memantine. In addition, the expression level of PEDF protein also increased by 1.8-fold at 2 days after the injection of memantine. Immunohistochemical study using anti-PEDF antibody showed that the majority of the PEDF-expressing cells were protoplasmic and perivascular astrocytes. Using a neurosphere assay, we confirmed that PEDF enhanced cellular proliferation under the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF) but was not involved in the multilineage potency of hippocampal progenitor cells. Over ...Continue Reading

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Citations

Nov 12, 2013·International Journal of Biological Macromolecules·Huijuan ZhangBaoguo Sun
May 7, 2013·Expert Opinion on Drug Discovery·Susan E CrawordOlga V Volpert
Feb 18, 2011·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Jean-Daniel AbrahamChantal Mourton-Gilles
Mar 9, 2013·Archives of Biochemistry and Biophysics·Srinivas RamasamySohail Ahmed
Apr 10, 2013·Toxicology Letters·Chaoxuan Dong, K J S Anand

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