Neuregulin1 attenuates cognitive deficits and hippocampal CA1 neuronal apoptosis partly via ErbB4 receptor in a rat model of chronic cerebral hypoperfusion
Neuregulin1 attenuates cognitive deficits and hippocampal CA1 neuronal apoptosis partly via ErbB4 receptor in a rat model of chronic cerebral hypoperfusion
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DOI：
10.1016/j.bbr.2019.02.046
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发表时间：
2019-06-03
影响因子：
2.7
通讯作者：
Liu, Weiping
中科院分区：
文献类型：
--
作者：
Hei, Yue;Chen, Rong;Liu, Weiping
神经调节蛋白1(NRG1)是一种有效的神经保护剂。我们先前的研究表明，在慢性脑低灌流(CCH)过程中，海马区NRG1/ErbB4的表达逐渐减少，并与神经细胞的凋亡相关。本研究旨在进一步探讨NRG1在CCH中的保护作用。用ErbB4受体拮抗剂AG1478研究ErbB4受体对NRG1NRG1‘S作用的影响。采用永久性双侧颈总动脉结扎(2VO)或假手术。脑室注射NRG1(100亩M)和AG1478(50 Mm)。术后8周用Morris水迷宫(MWM)和放射臂水迷宫(RAWM)检测大鼠认知功能障碍，并用Neun和TUNEL免疫组织化学方法检测大鼠海马CA1区神经元的存活和凋亡情况。Western blotting检测细胞凋亡相关蛋白表达及ErbB4活化(pErbB4/ErbB4)。结果表明，脑复康冲剂能明显改善大鼠的空间学习记忆和空间工作参考记忆能力，减轻海马神经元的丢失和凋亡，上调pErbB4/ErbB4和抗凋亡蛋白Bcl2的表达，下调促凋亡蛋白Caspase3和Bax的表达。此外，AG1478可部分消除NRG1的保护作用。综上所述，我们的研究表明，NRG1部分通过ErbB4受体改善CCH大鼠的认知功能障碍和神经细胞凋亡。
Neuregulin1 (NRG1) is an effective neuroprotectant. Previously we demonstrated that the expression of hippocampal NRG1/ErbB4 gradually decreased and correlates with neuronal apoptosis during chronic cerebral hypoperfusion (CCH). Here we aimed to further investigate the protective role of NRG1 in CCH. AG1478, an ErbB4 inhibitor, was used to explore the involvement of ErbB4 receptors in NRG1's action. Permanent bilateral common carotid artery occlusion (2VO) or sham operation was performed in Sprague-Dawley rats. NRG1 (100 mu M) and AG1478 (50 mM) was administered intraventricularly. Eight weeks post-surgery, cognitive impairment was analyzed using Morris water maze (MWM) and radial arm water maze (RAWM) tests, followed by histological assessment of the survival and apoptosis of hippocampal CA1 neurons using NeuN and TUNEL immunostaining respectively. Expression of apoptosis-related proteins and ErbB4 activation (pErbB4/ErbB4) was evaluated by Western blotting. The results showed that NRG1 significantly improved the performances in MWM (spatial learning and memory) and RAWM (spatial working and reference memory), attenuated hippocampal CM neuronal loss and apoptosis, upregulated the expression of pErbB4/ErbB4 and the anti-apoptotic protein Bcl-2, and downregulated the expression of pro-apoptotic proteins of Cleaved (Cl)-caspase3 and Bax. In addition, the protective effects of NRG1 could be partly abolished by AG1478. Taken together, our study suggested that NRG1 ameliorates cognitive impairment and neuronal apoptosis partly via ErbB4 receptors in rats with CCH.