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P1‐208: FGF2 REGULATES AMYLOID β SECRETIONS IN CULTURED OLIGODENDROCYTE PROGENITOR CELLS FROM THE ADULT RAT HIPPOCAMPUS
Author(s) -
Tatebayashi Yoshitaka,
Kikuchi-Nihonmatsu Naomi,
Matsuda Yoshiki,
Uchihara Toshiki
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.213
Subject(s) - amyloid precursor protein , progenitor cell , microbiology and biotechnology , oligodendrocyte , in vitro , in vivo , blot , hippocampus , intracellular , biology , transfection , chemistry , cell culture , endocrinology , medicine , biochemistry , stem cell , gene , central nervous system , alzheimer's disease , genetics , myelin , disease
Background:Progress in understanding the roles of adult oligodendrocyte (OL) lineage cells including OL progenitor cells (aOPCs) in the AD pathogenesis has been hampered by the lack of suitable culture techniques and in vivo markers. Last year, we reported a newly developed culture method for aOPCs from adult rat hippocampus and identified novel plexin-B3-expressing aOPCs as amyloid b (Ab)-secreting cells in vitro and in AD. Methods:Amyloid precursor protein (APP) metabolisms in cultured plexin-B3+ aOPCs were analyzed in detail by Western blotting, ELISA and g-secretase inhibitor DAPT. Results: FGF2 withdrawal increased numbers of plexin-B3+ aOPCs with increased Ab1-40, -42 secretions and Ab1-42/total Ab ratios. Intracellular APP-C83, and most likely APP-C89, two nonamyloidgenic substrates of g-secretase, accumulated in cultured aOPCs at 0 ng/ml FGF2 and these accumulations gradually diminished when FGF2 increased. In contrast, APP-C99, the amyloidgenic substrate of g-secretase that yields Abs, was barely detectable at lower concentrations of FGF2, becoming detectable as FGF2 increased. DAPT could not inhibit Ab secretions of aOPCs and was generally cytotoxic. Conclusions: FGF2 regulates natural Ab secretions of cultured aOPCs in a way different from that observed in conventional cultured models overexpressing APP and g-secretase.