Núcleo de Neurociências, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Brazil.
Neurobiol Learn Mem. 2012 Jan;97(1):113-23. doi: 10.1016/j.nlm.2011.10.003. Epub 2011 Oct 31.
It has been shown that the brain has its own intrinsic renin-angiotensin system (RAS) and angiotensin-(1-7) (Ang-(1-7)) is particularly interesting, because it appears to counterbalance most of the Ang II effects. Ang-(1-7) exerts its biological function through activation of the G-protein-coupled receptor Mas. Interestingly, hippocampus is one of the regions with higher expression of Mas. However, the role of Ang-(1-7)/Mas axis in hippocampus-dependent memories is still poorly understood. Here we demonstrated that Mas ablation, as well as the blockade of Mas in the CA1-hippocampus, impaired object recognition memory (ORM). We also demonstrated that the blockade of Ang II receptors AT1, but not AT2, recovers ORM impairment of Mas-deficient mice. Considering that high concentrations of Ang-(1-7) may activate AT1 receptors, nonspecifically, we evaluate the levels of Ang-(1-7) and its main precursors Ang I and Ang II in the hippocampus of Mas-deficient mice. The Ang I and Ang II levels are unaltered in the whole hipocampus of MasKo. However, Ang-(1-7) concentration is increased in the whole hippocampus of MasKo mice, as well as in the CA1 area. Taken together, our findings suggest that the functionality of the Ang-(1-7)/Mas axis is essential for normal ORM processing.
已经表明，大脑具有自身内在的肾素-血管紧张素系统（RAS），血管紧张素-（1-7）（Ang-（1-7））特别有趣，因为它似乎抵消了大多数 Ang II 的作用。Ang-（1-7）通过激活 G 蛋白偶联受体 Mas 发挥其生物学功能。有趣的是，海马体是 Mas 表达较高的区域之一。然而，Ang-（1-7）/Mas 轴在海马体依赖性记忆中的作用仍知之甚少。在这里，我们证明了 Mas 缺失以及 CA1-海马体中 Mas 的阻断会损害物体识别记忆（ORM）。我们还证明，阻断 Ang II 受体 AT1，但不是 AT2，可以恢复 Mas 缺陷型小鼠的 ORM 损伤。考虑到高浓度的 Ang-（1-7）可能非特异性地激活 AT1 受体，我们评估了 Mas 缺陷型小鼠海马体中 Ang-（1-7）及其主要前体 Ang I 和 Ang II 的水平。MasKo 小鼠整个海马体中的 Ang I 和 Ang II 水平没有改变。然而，Ang-（1-7）浓度在 MasKo 小鼠的整个海马体以及 CA1 区增加。总之，我们的发现表明 Ang-（1-7）/Mas 轴的功能对于正常的 ORM 处理是必不可少的。
