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J Neurosci:美学者揭示抗焦虑药或能阻止常见病毒引发出生缺陷

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摘要 : 2017年6月19日,国际著名神经科学学术期刊《The Journal of Neuroscience》杂志上在线发表了美国耶鲁大学医学院Anthony N. van den Pol研究员的一篇研究论文,论文报道了抗焦虑药能阻止一种常见病毒引发出生缺陷和耳聋。
2017年6月19日,国际著名神经科学学术期刊《The Journal of Neuroscience》杂志上在线发表了美国耶鲁大学医学院Anthony N. van den Pol研究员的一篇研究论文,论文报道了抗焦虑药能阻止一种常见病毒引发出生缺陷和耳聋。 每1000个婴儿中大约有4个会感染巨细胞病毒(CMV)。该病毒可导致癫痫和智力障碍以及包括小头畸形症在内的像寨卡一样的症状。CMV还会导致耳聋。它通常在怀孕期间被传给婴儿。一些婴儿生下来便有明显的感染迹象,有些直到后来才会发展出症状。 一种可在法国和意大利买到的抗焦虑药似乎能减少受感染小鼠体内的CMV水平。不过,目前尚不明确它是否会对大脑(CMV造成最大损伤的部位)产生类似效用。 Anthony Van den Pol及其团队向受感染小鼠体内注射了一日剂量的戊诺酰胺或者控制物质。“被注射了戊诺酰胺的小鼠更有可能幸存下来。它们活得更久,并且体重更沉——关于它们的一切事情看上去都更好一些。”Van den Pol表示。 当在“青少年期”接受评估时,接受过戊诺酰胺治疗的小鼠也未表现出在感染了CMV的对照小鼠中见到的异常社会反应和运动受损。在被称为星形胶质细胞(CMV攻击的目标)的人类脑细胞中开展的进一步试验显示,当这些细胞接受戊诺酰胺的治疗时,存在的病毒数量减少至原来的百分之一。 虽然一种名为更昔洛韦的药物可被用于一些人群来对抗CMV,但它不能给孕妇使用,因为该药物有导致出生缺陷的风险。 “目前没有针对CMV的疫苗。因此,不可能保护怀孕女性不受感染以及向未出生的婴儿转移。”英国卡迪夫大学CMV研究人员Ian Humphreys表示,“新的方法肯定是需要的。” 原文链接: Valnoctamide inhibits cytomegalovirus infection in developing brain and attenuates neurobehavioral dysfunctions and brain abnormalities 原文摘要: Cytomegalovirus (CMV) is the most common infectious cause of brain defects and neurological dysfunction in developing human babies. Due to the teratogenicity and toxicity of available CMV antivirals, treatment options during early development are markedly limited. Valnoctamide (VCD), a neuroactive mood stabilizer with no known teratogenic activity, was recently demonstrated to have anti-CMV potential. However, it is not known whether this can be translated into an efficacious therapeutic effect to improve CMV-induced adverse neurological outcomes. Using multiple models of CMV infection in the developing mouse brain, we show that subcutaneous low-dose VCD suppresses CMV by reducing virus available for entry into the brain, and by acting directly within the brain to block virus replication and dispersal. VCD during the first 3 weeks of life restored timely acquisition of neurological milestones in neonatal male and female mice and rescued long-term motor and behavioral outcomes in juvenile male mice. CMV-mediated brain defects, including decreased brain size, cerebellar hypoplasia, and neuronal loss, were substantially attenuated by VCD. No adverse side effects on neurodevelopment of uninfected control mice receiving VCD were detected. Treatment of CMV-infected human fetal astrocytes with VCD reduced both viral infectivity and replication by blocking viral particle attachment to the cell, a mechanism that differs from available anti-CMV drugs. These data suggest that VCD during critical periods of neurodevelopment can effectively suppress CMV replication in the brain and safely improve both immediate and long-term neurological outcomes. doi:10.1523/JNEUROSCI.0970-17.201 作者:Anthony N. van den P 点击:
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