Therapeutic potentials of neural stem cells treated with fluoxetine in Alzheimer's disease

被引:27
作者
Chang, Keun-A
Kim, Jeong A.
Kim, Saeromi
Joo, Yuyoung
Shin, Ki Young
Kim, Seonghan
Kim, Hye-Sun
Suh, Yoo-Hun [1 ]
机构
[1] Seoul Natl Univ, Coll Med, Dept Pharmacol, Seoul 110799, South Korea
基金
新加坡国家研究基金会;
关键词
Alzheimer's disease; Fetal neural stem cells; Amy told beta; Proliferation; Differentiation; Fluoxetine; FIBROBLAST-GROWTH-FACTOR; PROGENITOR CELLS; SUBVENTRICULAR ZONE; NEURONAL PRECURSORS; NEUROTROPHIC FACTOR; GENERATED NEURONS; NERVOUS-SYSTEM; DENTATE GYRUS; ADULT BRAIN; DIFFERENTIATION;
D O I
10.1016/j.neuint.2012.03.017
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recent studies have proposed that chronic treatment with antidepressants increases neurogenesis in the adult hippocampus. However, the effect of antidepressants on fetal neural stem cells (NSCs) has not been well defined. Our study shows the dose-dependent effects of fluoxetine on the proliferation and neural differentiation of NSCs. Fluoxetine, even at nanomolar concentrations, stimulated proliferation of NSCs and increased the number of beta III-tubulin (Tuj 1)- and neural nucleus marker (NeuN)-positive cells, but not glial fibrillary acidic protein (GFAP)-positive cells. These results suggest that fluoxetine can enhance neuronal differentiation. In addition, fluoxetine has protective effects against cell death induced by oligomeric amyloid beta (A beta(42)) peptides. Taken together, these results clearly show that fluoxetine promotes both the proliferation and neuronal differentiation of NSCs and exerts protective effects against A beta(42)-induced cytotoxicities in NSCs, which suggest that the use of fluoxetine is applicable for cell therapy for various neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases by its actions in NSCs. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码:885 / 891
页数:7
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