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研究揭示中颞叶癫痫患者的成体神经发生和胶质生成的改变
2022-04-10 13:24

美国南加州大学Michael A. Bonaguidi研究小组揭示中颞叶癫痫患者的成体神经发生和胶质生成的改变。相关论文于2022年4月5日在线发表于国际学术期刊《自然—神经科学》。

研究人员表示,海马是人们最常见的癫痫病灶。在海马中,异常的神经发生在啮齿类动物模型中的癫痫的启动和进展中起着关键作用,但这在人类中是否也是如此尚不清楚。
 
为了解决这个问题,研究人员对健康海马和中颞叶癫痫(MTLE)的手术切除物进行了免疫荧光,加上神经干细胞培养和体外海马片的多电极记录。研究人员发现,癫痫的持续时间较长,与神经元的生产急剧下降和星形细胞生成的持续数量有关。此外,MTLE中不成熟的神经元大多不活跃,在有局部癫痫样活动的病例中也观察不到。然而,未成熟的星形胶质细胞存在于每个MTLE病例中,其位置和活动取决于癫痫样活动。因此,不成熟的星形胶质细胞,而不是新生的神经元,代表了一个潜在的靶标,可以持续地调节成年人类神经元的过度活动。
 
附:英文原文

Title: Altered adult neurogenesis and gliogenesis in patients with mesial temporal lobe epilepsy

Author: Ammothumkandy, Aswathy, Ravina, Kristine, Wolseley, Victoria, Tartt, Alexandria N., Yu, Pen-Ning, Corona, Luis, Zhang, Naibo, Nune, George, Kalayjian, Laura, Mann, J. John, Rosoklija, Gorazd B., Arango, Victoria, Dwork, Andrew J., Lee, Brian, Smith, J. A. D., Song, Dong, Berger, Theodore W., Heck, Christianne, Chow, Robert H., Boldrini, Maura, Liu, Charles Y., Russin, Jonathan J., Bonaguidi, Michael A.

Issue&Volume: 2022-04-05

Abstract: The hippocampus is the most common seizure focus in people. In the hippocampus, aberrant neurogenesis plays a critical role in the initiation and progression of epilepsy in rodent models, but it is unknown whether this also holds true in humans. To address this question, we used immunofluorescence on control healthy hippocampus and surgical resections from mesial temporal lobe epilepsy (MTLE), plus neural stem-cell cultures and multi-electrode recordings of ex vivo hippocampal slices. We found that a longer duration of epilepsy is associated with a sharp decline in neuronal production and persistent numbers in astrogenesis. Further, immature neurons in MTLE are mostly inactive, and are not observed in cases with local epileptiform-like activity. However, immature astroglia are present in every MTLE case and their location and activity are dependent on epileptiform-like activity. Immature astroglia, rather than newborn neurons, therefore represent a potential target to continually modulate adult human neuronal hyperactivity. The authors identify adult neurogenesis in individuals with epilepsy that declines with disease duration and epileptiform activity. Additionally, astrogenesis persists and immature astrocyte activity is inversely associated with neuronal hyperactivity.

DOI: 10.1038/s41593-022-01044-2

Source: https://www.nature.com/articles/s41593-022-01044-2

Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新IF:28.771
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex


本期文章:《自然—神经科学》:Online/在线发表

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