Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Neurorestoration Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Nat Neurosci. 2022 Apr;25(4):493-503. doi: 10.1038/s41593-022-01044-2. Epub 2022 Apr 5.
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.
海马体是人类中最常见的癫痫发作部位。在啮齿动物模型中，海马体中的异常神经发生在癫痫的发生和发展中起着关键作用，但尚不清楚这是否也适用于人类。为了解决这个问题，我们使用免疫荧光法对正常健康的海马体和内侧颞叶癫痫（MTLE）的手术切除标本进行了研究，同时还进行了神经干细胞培养和离体海马切片的多电极记录。我们发现，癫痫持续时间较长与神经元生成急剧下降和星形胶质细胞持续增加有关。此外，MTLE 中的不成熟神经元大多处于静止状态，在局部癫痫样活动的病例中观察不到。然而，在每个 MTLE 病例中都存在不成熟的星形胶质细胞，它们的位置和活性依赖于癫痫样活动。因此，不成熟的星形胶质细胞而不是新生神经元代表了一个潜在的目标，可以持续调节成人的神经元过度兴奋。
