Memory & Brain Research Center, Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Cell Rep. 2019 Jun 25;27(13):3741-3751.e4. doi: 10.1016/j.celrep.2019.05.101.
Adult hippocampal neurogenesis has been reported to be decreased, increased, or not changed in Alzheimer's disease (AD) patients and related transgenic mouse models. These disparate findings may relate to differences in disease stage, or the presence of seizures, which are associated with AD and can stimulate neurogenesis. In this study, we investigate a transgenic mouse model of AD that exhibits seizures similarly to AD patients and find that neurogenesis is increased in early stages of disease, as spontaneous seizures became evident, but is decreased below control levels as seizures recur. Treatment with the antiseizure drug levetiracetam restores neurogenesis and improves performance in a neurogenesis-associated spatial discrimination task. Our results suggest that seizures stimulate, and later accelerate the depletion of, the hippocampal neural stem cell pool. These results have implications for AD as well as any disorder accompanied by recurrent seizures, such as epilepsy.
成人海马神经发生在阿尔茨海默病（AD）患者和相关的转基因小鼠模型中被报道减少、增加或不变。这些不同的发现可能与疾病阶段的差异或与 AD 相关的癫痫发作的存在有关，癫痫发作可以刺激神经发生。在这项研究中，我们研究了一种表现出类似 AD 患者癫痫发作的 AD 转基因小鼠模型，发现神经发生在疾病的早期阶段增加，因为自发癫痫发作变得明显，但随着癫痫发作的复发，神经发生减少到低于对照水平。用抗癫痫药物左乙拉西坦治疗可恢复神经发生并改善与神经发生相关的空间辨别任务的表现。我们的结果表明，癫痫发作刺激，随后加速了海马神经干细胞池的耗竭。这些结果对 AD 以及任何伴有复发性癫痫发作的疾病（如癫痫）都有影响。
