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δ-阿片受体过表达对缺氧时大脑皮质GABAA受体α1亚基表达的影响

Effect of delta-opioid receptor over-expression on cortical expression of GABAA receptor alpha1-subunit in hypoxia.

作者信息

Feng Yuan, He Xiaozhou, Yang Yilin, Chen Jingshan, Yin Kaisheng, Xia Ying

机构信息

First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.

出版信息

Chin J Physiol. 2011 Apr 30;54(2):118-23. doi: 10.4077/cjp.2011.amm047.

DOI:10.4077/cjp.2011.amm047
PMID:21789893
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3371375/
Abstract

Recent studies show that both delta-opioid receptors (DOR) and GABA receptors play a neuroprotective role in the mature cortex. Since we have observed that DOR over-expression renders the cortex more tolerant to hypoxic stress, we asked whether DOR over-expression affects GABA receptors expression in the cortex under hypoxia. As the first step, we investigated the expression of GABAA receptor alpha1-subunit (GABAA Ralpha1, the most abundant alpha-subunit of GABA receptors in the adult brain) in the mouse cortex with transgenic DOR over-expression after hypoxia. The results showed that GABAA Ralpha1 expression was lower in the transgenic than wild-type cortex, suggesting that DOR overexpression induces an inhibitory effect on GABAA receptor expression. Hypoxia for 1-3 days significantly increased GABAA Ralpha1 expression in the wild-type cortex, which may be an adaptive strategy for protecting the cortex against hypoxic stress. Interestingly, such increase was not found in the transgenic cortex with DOR over-expression. This may represent an interactive regulation in the transgenic cortex to efficiently balance energy production and consumption for better adaptation to hypoxic environment. Since DOR over-expression increases cortical tolerance to hypoxia, an increase in GABA receptors expression (an energy-costing process) may not be necessary in the cortex with DOR over-expression.

摘要

最近的研究表明,δ-阿片受体(DOR)和GABA受体在成熟皮层中均发挥神经保护作用。由于我们观察到DOR过表达使皮层对缺氧应激更具耐受性,我们不禁要问,DOR过表达是否会影响缺氧条件下皮层中GABA受体的表达。作为第一步,我们研究了缺氧后过表达转基因DOR的小鼠皮层中GABAA受体α1亚基(GABAA Rα1,成人大脑中GABA受体中最丰富的α亚基)的表达。结果显示,转基因皮层中GABAA Rα1的表达低于野生型皮层,这表明DOR过表达对GABAA受体表达产生抑制作用。缺氧1至3天显著增加了野生型皮层中GABAA Rα1的表达,这可能是保护皮层免受缺氧应激的一种适应性策略。有趣的是,在过表达DOR的转基因皮层中未发现这种增加。这可能代表了转基因皮层中的一种相互作用调节,以有效平衡能量产生和消耗,从而更好地适应缺氧环境。由于DOR过表达增加了皮层对缺氧的耐受性,在过表达DOR的皮层中,可能无需增加GABA受体表达(一个耗能过程)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a5/3371375/ffa78ab68bc3/nihms362459f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a5/3371375/e9d19a31c007/nihms362459f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a5/3371375/8b45b59bd54a/nihms362459f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a5/3371375/35d90a29a6a8/nihms362459f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a5/3371375/ffa78ab68bc3/nihms362459f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a5/3371375/e9d19a31c007/nihms362459f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a5/3371375/8b45b59bd54a/nihms362459f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a5/3371375/35d90a29a6a8/nihms362459f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a5/3371375/ffa78ab68bc3/nihms362459f4.jpg

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delta-Opioid receptor antagonism induces NMDA receptor-dependent excitotoxicity in anoxic turtle cortex.δ-阿片受体拮抗作用在缺氧海龟皮层中诱导NMDA受体依赖性兴奋性毒性。
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Delta 2-specific opioid receptor agonist and hibernating woodchuck plasma fraction provide ischemic neuroprotection.
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