Neurosteroid estradiol rescues ischemia-induced deficit in the long-term potentiation, of rat hippocampal CA1 neurons
Neurosteroid estradiol rescues ischemia-induced deficit in the long-term potentiation, of rat hippocampal CA1 neurons
复制标题
DOI：
10.1016/j.neuropharm.2006.11.012
复制
发表时间：
2007-03-01
影响因子：
4.7
通讯作者：
Sokabe, Masahiro
中科院分区：
文献类型：
--
作者：
Dai, Xiaoniu;Chen, Ling;Sokabe, Masahiro
越来越多的证据表明，神经甾体17 β-雌二醇（E2），一种女性性激素，对脑损伤具有神经保护作用。然而，它仍然是未知的，是否E2也可以保护海马CA 1区神经元的功能缺陷，在突触传递和可塑性造成的缺血。为了解决这个问题，成年雄性Wistar大鼠进行轻度全脑缺血四血管闭塞（4VO）10分钟，和E2的管理对缺血性损伤的影响进行了研究。缺血7天后，通过应用实时光学记录技术对用电压敏感染料（RH 482）染色的海马切片进行检查Schaffer侧支-CA 1突触的电生理特性。缺血性脑表现出基础突触传递减少和UP诱导受损，但对脉冲易化无改变。缺血前3 h给予E2（1 mg/kg）可保护CA 1区神经元免受缺血诱导的突触功能障碍。雌激素受体-α（ER α）选择性激动剂丙基吡唑三醇（PPT，2 mg/kg）具有类似的保护作用，但雌激素受体-β（ER β）激动剂二芳基丙腈（DPN，8 mg/kg）则没有这种作用。组织学检查显示，短暂性全脑缺血显著降低了CA 1区锥体神经元的密度。细胞损失显着衰减E2和PPT，但不DPN，观察突触功能。这些结果表明，E2不仅可以保护神经元免于细胞死亡，而且可以保护神经元免于由于相对轻度的短暂性脑缺血而引起的功能损伤，并且这种作用是由ER α介导的，而不是由ER β介导的。(c)2006爱思唯尔有限公司保留所有权利。
Increasing evidence indicates that neurosteroid 17 beta-Estradiol (E2), a type of female sex hormone, has a neuroprotective effect against cerebral injury. However, it remains unknown whether E2 can also protect the hippocampal CA1 neurons from functional deficits in synaptic transmission and plasticity caused by ischemia. To address this issue, adult mate Wistar rats were subjected to mild global cerebral ischemia created by four-vessel occlusion (4VO) for 10 min, and the effects of E2 administration against the ischemic injury were investigated. The electrophysiological properties of Schaffer collateral-CA1 synapses were examined 7 days after ischemia by applying a real-time optical recording technique to the hippocampal slices stained with a voltage-sensitive dye (RH482). The ischemic brain showed a decreased basal synaptic transmission and an impairment of UP induction, but no alteration in paired-pulse facilitation. The administration of E2 (1 mg/kg) 3 h before ischemia was able to protect CA1 neurons from these ischemia-induced synaptic dysfunctions. The estrogen receptor-alpha (ER alpha) selective agonist, propyl pyrazole triol (PPT, 2 mg/kg), exerted a similar protective effect, but the estrogen receptor-beta (ER beta) agonist, diarylpropiolnitrile (DPN, 8 mg/kg), failed to do so. A histological examination revealed that the transient global cerebral ischemia markedly reduced the density of pyramidal neurons in the CA1 region. The cell loss was significantly attenuated by E2 and PPT but not by DPN, as observed in synaptic functions. These findings suggest that E2 can protect neurons not only from cell death but also from functional damages due to a relatively mild degree of transient cerebral ischemia, and this effect is mediated by ER alpha, but not by ER beta. (c) 2006 Elsevier Ltd. All rights reserved.