Limited influence of olanzapine on adult forebrain neural precursors in vitro
Limited influence of olanzapine on adult forebrain neural precursors in vitro
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DOI：
10.1016/j.neuroscience.2006.02.014
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
LaMantia, A. -S.
中科院分区：
文献类型：
--
作者：
Councill, J. H.;Tucker, E. S.;LaMantia, A. -S.
我们评估了非典型抗精神病药物奥氮平对体外成人神经前体细胞分化和基因表达的影响。从前脑室下区（SVZ）衍生的神经球获得的神经前体表达已知以高至中等亲和力结合奥氮平的受体子集（13/24）;相反，所有24种受体均在SVZ中表达。在存在10 nM、100 nM或1 μ M奥氮平的情况下，由神经球前体生成的少突胶质细胞、神经元、GABA能神经元和星形胶质细胞的频率无显著变化。同时，基于溴脱氧尿苷掺入，奥氮平对细胞增殖的反应没有明显变化。对药物的反应在细胞学分化方面没有重大变化;然而，在一个浓度（10 nM）下，来自神经球前体的胶质细胞酸性蛋白标记的星形胶质细胞的大小有一个小的但具有统计学意义的增加。此外，奥氮平明显调节一种5-羟色胺受体-5 HT 2A-在分化的神经球文化的表达，但是，它不修改其他几个受体或精神分裂症易感基因的表达。因此，奥氮平对体外成体神经前体细胞的分化和基因表达的影响有限。(c)2006年IBRO。由爱思唯尔有限公司出版。保留所有权利。
We evaluated the activity of the atypical antipsychotic drug olanzapine on differentiation and gene expression in adult neural precursor cells in vitro. Neural precursors obtained from forebrain subventricular zone (SVZ)-derived neurospheres express a subset (13/24) of receptors known to bind olanzapine at high to intermediate affinities; in contrast, all 24 are expressed in the SVZ. In the presence of 10 nM, 100 nM or 1 mu M olanzapine, there is no significant change in the frequency of oligodendrocytes, neurons, GABAergic neurons and astrocytes generated from neurosphere precursors. In parallel, there is no apparent change in cell proliferation in response to olanzapine, based upon bromodeoxyuridine incorporation. There are no major changes in cytological differentiation in response to the drug; however, at one concentration (10 nM) there is a small but statistically significant increase in the size of glial fibrillary acidic protein-labeled astrocytes derived from neurosphere precursors. In addition, olanzapine apparently modulates expression of one serotonin receptor-5HT2A-in differentiating neurosphere cultures; however, it does not modify expression of several other receptors or schizophrenia vulnerability genes. Thus, olanzapine has a limited influence on differentiation and gene expression in adult neural precursor cells in vitro. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.