Feng Yuan, He Xiaozhou, Yang Yilin, Chen Jingshan, Yin Kaisheng, Xia Ying
First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
Chin J Physiol. 2011 Apr 30;54(2):118-23. doi: 10.4077/cjp.2011.amm047.
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.
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)。