Sex-different effect of angiotensin II type 2 receptor on ischemic brain injury and cognitive function
Sex-different effect of angiotensin II type 2 receptor on ischemic brain injury and cognitive function
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DOI：
10.1016/j.brainres.2009.08.068
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发表时间：
2009-11-10
期刊：
影响因子：
2.9
通讯作者：
Horiuchi, Masatsugu
中科院分区：
文献类型：
--
作者：
Sakata, Akiko;Mogi, Masaki;Horiuchi, Masatsugu
我们先前报道血管紧张素II 2型(AT(2))受体信号通路对局灶性脑缺血后的神经损伤和认知功能障碍有保护作用。我们利用AT(2)受体缺陷小鼠(Agtr2(-))研究了AT(2)受体在性别差异中的可能作用，重点是认知功能和缺血性脑损伤。与雄性Aytr2(-)和雌性野生型(Agtr2(+))相比，雌性Agtr2(-)在Morris水迷宫测试中空间记忆能力受损，而Agtr2(+)无明显性别差异。有趣的是，溴脱氧尿嘧啶核苷掺入试验显示，女性Agtr2(-)组的海马神经发生明显低于女性Agtr2(+)组。而Agtr2(-)组大鼠大脑中动脉(MCA)闭塞后缺血面积较雌性组显著增加，而Agtr2(+)组无明显性别差异。与雌性Agtr2(-)小鼠相比，雄性Agtr2(-)小鼠大脑中动脉闭塞24小时后，同侧脑组织AT受体表达增加，脑血流量(CBF)明显受损。总而言之，AT(2)受体的缺失表现出不同性别的影响，例如女性的严重认知障碍和男性的脑缺血损伤，其中女性的海马神经发生减少，而男性的脑缺血损伤更严重，脑血流减少。(C)2009爱思唯尔B.V.保留所有权利。
We previously reported that angiotensin II type 2 (AT(2)) receptor signaling prevents neural damage and cognitive impairment after focal cerebral ischemia. We investigated the possible roles of the AT(2) receptor in the sex difference, focusing on cognitive function and ischemic brain damage using AT(2) receptor-deficient mice (Agtr2(-)). In Agtr2(-), spatial memory evaluated by the Morris water maze test was impaired in female compared with that in male Aytr2(-) and female wild-type (Agtr2(+)), while no significant sex-different change was observed in Agtr2(+). Interestingly, bromodeoxyuridine incorporation assay showed a significant decrease of hippocampal neurogenesis in female Agtr2(-) compared with that in female Agtr2(+). In contrast, ischemic area after middle cerebral artery (MCA) occlusion was significantly increased in male compared with female mice in Agtr2(-), while no significant sex-different change was observed in Agtr2(+). Male Agtr2(-) mice showed higher AT, receptor expression and significantly impaired cerebral blood flow (CBF) in the ipsilateral side 24 hours after MCA occlusion compared with female Agtr2(-) mice. In conclusion, deletion of the AT(2) receptor showed a sex-different effect such as a severe cognitive impairment with a decrease of hippocampal neurogenesis in females and a larger ischemic brain damage with a decrease of CBF in males. (C) 2009 Elsevier B.V. All rights reserved.