ABC transporters B1, C1 and G2 differentially regulate neuroregeneration in mice.
ABC transporters B1, C1 and G2 differentially regulate neuroregeneration in mice.
复制标题
DOI：
10.1371/journal.pone.0035613
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Pahnke J
中科院分区：
文献类型：
--
作者：
Schumacher T;Krohn M;Hofrichter J;Lange C;Stenzel J;Steffen J;Dunkelmann T;Paarmann K;Fröhlich C;Uecker A;Plath AS;Sommer A;Brüning T;Heinze HJ;Pahnke J
ATP结合盒（ABC）转运蛋白是机体内环境稳定的重要调节因子，在保护机体免受潜在有害的外源性物质的侵害方面尤为重要。最近，越来越多的体外观察表明ABC转运蛋白在干细胞的分化和维持中的功能作用。因此，我们试图确定缺乏不同ABC转运蛋白（ABCB 1，ABCG 2或ABCC 1）表达的动物的脑相关表型变化。在体内分析ABC转运蛋白缺陷动物和体外神经干/祖细胞的成年神经发生导致复杂的结果。在体内，ABC转运蛋白缺陷小鼠（ABCB 10/0）中神经元祖细胞的分化受到阻碍，表现为双皮质素+（−36%）和钙视网膜蛋白+（−37%）细胞数量减少。在体外，我们证实了这一发现与单个神经干/祖细胞（NSPCs）的功能丧失无关。此外，对活动、探索行为和焦虑水平的评估显示，ABCB 10/0和ABCC 10/0小鼠的行为发生了变化，而ABCG 20/0小鼠则基本不受影响。我们的数据表明，单一的ABC转运蛋白缺陷并不一定会损害神经元祖细胞的稳态在单一的NSPC水平，如以前的研究所建议的。然而，不同的ABC转运蛋白的损失影响全球脑内稳态，具有广泛的后果，导致体内神经源性功能受损，甚至导致不同的行为表型。除了已知的ABC转运蛋白在蛋白质病如帕金森病和阿尔茨海默病中的作用外，我们的数据还突出了了解ABC转运蛋白对大脑稳态和再生潜力的一般功能的重要性。
ATP-binding cassette (ABC) transporters are essential regulators of organismic homeostasis, and are particularly important in protecting the body from potentially harmful exogenous substances. Recently, an increasing number of in vitro observations have indicated a functional role of ABC transporters in the differentiation and maintenance of stem cells. Therefore, we sought to determine brain-related phenotypic changes in animals lacking the expression of distinct ABC transporters (ABCB1, ABCG2 or ABCC1). Analyzing adult neurogenesis in ABC transporter-deficient animals in vivo and neuronal stem/progenitor cells in vitro resulted in complex findings. In vivo, the differentiation of neuronal progenitors was hindered in ABC transporter-deficient mice (ABCB10/0) as evidenced by lowered numbers of doublecortin+ (−36%) and calretinin+ (−37%) cells. In vitro, we confirmed that this finding is not connected to the functional loss of single neural stem/progenitor cells (NSPCs). Furthermore, assessment of activity, exploratory behavior, and anxiety levels revealed behavioral alterations in ABCB10/0 and ABCC10/0 mice, whereas ABCG20/0 mice were mostly unaffected. Our data show that single ABC transporter-deficiency does not necessarily impair neuronal progenitor homeostasis on the single NSPC level, as suggested by previous studies. However, loss of distinct ABC transporters impacts global brain homeostasis with far ranging consequences, leading to impaired neurogenic functions in vivo and even to distinct behavioral phenotypes. In addition to the known role of ABC transporters in proteopathies such as Parkinson's disease and Alzheimer's disease, our data highlight the importance of understanding the general function of ABC transporters for the brain's homeostasis and the regeneration potential.
登录
查看更多内容
影响因子：
4.2
作者：
Kernie, SG;Erwin, TM;Parada, LF
通讯作者：
Parada, LF
影响因子：
3.2
作者：
Ferreira, Mario Jose;de Sa-Nogueira, Isabel
通讯作者：
de Sa-Nogueira, Isabel
影响因子：
82.9
作者：
Holcomb, L;Gordon, MN;Duff, K
通讯作者：
Duff, K
影响因子：
4.2
作者：
Bye, Nicole;Carron, Sarah;Morganti-Kossmann, M. Cristina
通讯作者：
Morganti-Kossmann, M. Cristina
影响因子：
--
作者：
Ferrari, Daniela;Binda, Elena;Vescovi, Angelo Luigi
通讯作者：
Vescovi, Angelo Luigi