title: Protection of Radial Glial-Like Cells in the Hippocampus of APP/PS1 Mice: a Novel Mechanism of Memantine in the Treatment of Alzheimer's Disease.
abstract: The failure of adult neurogenesis in the hippocampal dentate gyrus (DG) is closely correlated with memory decline in Alzheimer's disease (AD). Radial glial-like cells (RGLs) localized to the adult DG generate intermediate progenitor cells and immature neurons and thus contribute to adult hippocampus neurogenesis. Memantine (MEM) has been indicated to dramatically increase hippocampal neurogenesis by promoting the proliferation of RGLs. In this study, we examined the effect of MEM on the capacity for hippocampal cell proliferation and the amount of RGLs in APPswe/PS1∆E9 transgenic (APP/PS1) mice between 9 and 13 months of age. MEM could enhance hippocampal neurogenesis and increase the number of RGLs in the DG subgranular zone (DG-SGZ) of APP/PS1 mice of both ages. Moreover, MEM decreased amyloidogenesis in 13-month-old APP/PS1 mice and protected cultured radial glia cells (RGCs, L2.3 cells) from apoptosis induced by the β amyloid peptide (Aβ). Additionally, MEM inhibited microglial activation in a vertical process in DG-SGZ of APP/PS1 mice and decreased interacting with RGL processes. Reelin is involved in the proliferation of RGLs in the hippocampus, which was typically upregulated in the hippocampus of APP/PS1 mice by MEM and thought to be an active signaling pathway associated with the MEM-induced increase in RGLs. Our data suggest a previously uncharacterized role for MEM in treating AD.
authors.affiliation: Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Dayu
authors.initials: D
authors.lastname: Sun
authors.forename: Junhua
authors.initials: J
authors.lastname: Chen
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Bao
authors.forename: Yulong
authors.initials: Y
authors.lastname: Cai
authors.forename: Jinghui
authors.initials: J
authors.lastname: Zhao
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Fan
authors.forename: Haiwei
authors.initials: H
authors.lastname: Xu
mesh_terms: D000375:Aging / Q000473:pathology; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002460:Cell Line; D018891:Dentate Gyrus / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008559:Memantine / Q000494:pharmacology / Q000627:therapeutic use*; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000473:pathology*; D000066829:Neuroprotection / Q000187:drug effects; D058225:Plaque, Amyloid / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics*; D000091042:Reelin Protein; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D015816:Cell Adhesion Molecules, Neuronal; C498794:Disc1 protein, mouse; D016326:Extracellular Matrix Proteins; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D053764:Presenilin-1; D000091042:Reelin Protein; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D001973:Bromodeoxyuridine; D008559:Memantine