Prenatal exposure to buprenorphine renders offspring vulnerable to cerebral impairments. In this study, our data demonstrate, for the first time, that prenatal exposure to buprenorphine escalates astrocyte activation concurrent with indications of endoplasmic reticulum (ER) stress in the hippocampi of neonates, and this can be prevented by the coadministration of dextromethorphan with buprenorphine. Furthermore, dextromethorphan can inhibit the accumulation of GPR37 in the hippocampus of newborns caused by buprenorphine and is accompanied by the proapoptotic ER stress response that involves the procaspase-3/CHOP pathway. Primary astrocyte cultures derived from the neonates of the buprenorphine group also displayed aberrant ER calcium mobilization and elevated basal levels of cyclooxygenase-2 (COX-2) at 14 days in vitro while showing sensitivity to lipopolysaccharide-activated expression of COX-2. Similarly, these long-lasting defects in the hippocampus and astrocytes were abolished by dextromethorphan. Our findings suggest that prenatal exposure to buprenorphine might instigate long-lasting effects on hippocampal and astrocytic functions. The beneficial effects of prenatal coadministration of dextromethorphan might be, at least in part, attributed to its properties in attenuating astrocyte activation and hippocampal ER stress in neonates.

中文翻译：

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右美沙芬抑制产前接触丁丙诺啡引起的新生儿星形胶质细胞活化和内质网应激

产前接触丁丙诺啡会使后代容易出现脑损伤。在这项研究中，我们的数据首次表明，产前接触丁丙诺啡会增加星形胶质细胞活化，同时出现新生儿海马内质网 (ER) 应激的迹象，而这可以通过将右美沙芬与丁丙诺啡共同给药来预防。此外，右美沙芬可以抑制丁丙诺啡引起的新生儿海马中 GPR37 的积累，并伴有涉及 procaspase-3/CHOP 通路的促凋亡 ER 应激反应。来自丁丙诺啡组新生儿的原代星形胶质细胞培养物在体外14 天时也显示出异常的 ER 钙动员和升高的环氧合酶-2 (COX-2) 基础水平同时对脂多糖激活的 COX-2 表达表现出敏感性。同样，右美沙芬消除了海马体和星形胶质细胞中这些长期存在的缺陷。我们的研究结果表明，产前接触丁丙诺啡可能会对海马和星形胶质细胞功能产生长期影响。产前同时服用右美沙芬的有益效果可能至少部分归因于其在减轻新生儿星形胶质细胞活化和海马内质网应激方面的特性。