Effects of the angiotensin-(1-7) receptor Mas on cell proliferation and on the population of doublecortin positive cells within the dentate gyrus and the piriform cortex
Effects of the angiotensin-(1-7) receptor Mas on cell proliferation and on the population of doublecortin positive cells within the dentate gyrus and the piriform cortex
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DOI：
10.1016/j.euroneuro.2013.06.004
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发表时间：
2014-02-01
影响因子：
5.6
通讯作者：
Halbach, O. von Bohlem Und
中科院分区：
文献类型：
--
作者：
Freund, M.;Walther, T.;Halbach, O. von Bohlem Und
除了众所周知的具有生物活性的血管紧张素II外，还发现了其他具有生物活性的血管紧张素，包括血管紧张素IV和血管紧张素-(1-7)。几年前，我们和其他人发现Mas原癌基因编码一种G蛋白偶联受体，该受体对血管紧张素-(1-7)信号传导至关重要。Mas不仅在外周表达，也在大脑内部表达，如齿状回（DG）和梨状皮质（PC）。由于DG具有成体神经发生的能力，我们研究了Mas缺失对成体神经发生的影响。Mas的缺失不会改变成年DG的细胞增殖（用磷酸组蛋白H3监测），也不会改变细胞死亡（用活化的Caspase 3监测）。然而，Mas缺乏导致双皮质素（DCX）阳性细胞数量增加，表明缺乏Mas增加了该细胞群的数量。关于PC，讨论了该区域是否在生理条件下发生成人神经发生。我们可以证明Mas缺乏对细胞分裂和PC内dcx阳性细胞的数量有影响。由于Mas在出生前在大脑中不表达，我们的数据可能表明，成人海马神经发生和产前发育期间发生的神经发生有几个共同的机制，但至少在部分上是不同的。此外，由于Mas的缺乏增加了dcx阳性年轻神经元的数量，因此Mas的阻断可能有利于刺激成人的神经发生。(C) 2013 Elsevier B.V. and ECNP版权所有
Aside from the well-known biologically active angiotensin II, other biologically active angiotensins have been discovered, including angiotensin IV and angiotensin-(1-7). Some years ago, we and others discovered that the Mas proto-oncogene encodes a G protein-coupled receptor being essential for angiotensin-(1-7) signaling. Mas is not only expressed in the periphery but also within the brain, e.g. in the dentate gyrus (DG) and the piriform cortex (PC). Since the DG is capable of adult neurogenesis, we examined the impact of a deletion of Mas upon adult neurogenesis. Deletion of Mas did not alter cell proliferation in the adult DG (as monitored with phosphohistone H3) and did not alter cell death (as monitored with activated Caspase 3). However, Mas deficiency resulted in an increase in the number of doublecortin (DCX) positive cells, indicating that lack of Mas increases the number of this cell population. Concerning the PC, it is discussed whether adult neurogenesis occurs under physiological conditions in this area. We could demonstrate that Mas deficiency has an impact on cell division and on the population of DCX-positive cells within the PC. Since Mas is not expressed before birth within the brain, our data may suggest that adult hippocampal neurogenesis and neurogenesis occurring during prenatal development share several common mechanisms, but are, at least in part, differentially regulated. Moreover, since deficiency for Mas increases the numbers of DCX-positive young neurons, blockage of Mas might be beneficial in stimulating neurogenesis in adults. (C) 2013 Elsevier B.V. and ECNP All rights reserved.