tau 病 THY-Tau22 小鼠模型中的过度兴奋和癫痫发作。
Hyperexcitability and seizures in the THY-Tau22 mouse model of tauopathy.
机构信息
University of Lille, Inserm, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, Lille, France; Alzheimer & Tauopathies, LabEx DISTALZ, LiCEND, Lille, France.
Department of Anesthesiology and Perioperative Medicine, Oregon Health and Sciences University, Portland, OR, USA.
出版信息
Neurobiol Aging. 2020 Oct;94:265-270. doi: 10.1016/j.neurobiolaging.2020.06.004. Epub 2020 Jun 20.
Epileptic seizures constitute a significant comorbidity of Alzheimer's disease (AD), which are recapitulated in transgenic mouse models of amyloidogenesis. Here, we sought to evaluate the potential role of tau pathology regarding seizure occurrence. To this end, we performed intra-hippocampal electroencephalogram (EEG) recordings and PTZ (pentylenetetrazol) seizure threshold tests in THY-Tau22 transgenic mice of AD-like tau pathology. We demonstrate that despite a lack of spontaneous epileptiform activity in Tau22 mice, the animals display increased PTZ-induced seizure susceptibility and mortality. The increased propensity for induced seizures in THY-Tau22 mutants correlates with astrogliosis and increased expression of adenosine kinase, consistent with increased network excitability. These data support an impact of tau pathology toward AD-associated seizures and suggest that tau pathology may contribute to seizure generation in AD independent of Aβ pathology.
癫痫发作是阿尔茨海默病（AD）的一种严重合并症，在淀粉样蛋白发生的转基因小鼠模型中得到了重现。在这里，我们试图评估tau 病理学在癫痫发作发生中的潜在作用。为此，我们在具有 AD 样 tau 病理学的 THY-Tau22 转基因 AD 小鼠中进行了海马内脑电图（EEG）记录和 PTZ（戊四氮）癫痫发作阈值测试。我们证明，尽管 Tau22 小鼠没有自发的癫痫样活动，但这些动物表现出增加的 PTZ 诱导的癫痫易感性和死亡率。THY-Tau22 突变体中诱导性癫痫发作的增加倾向与星形胶质细胞增生和腺苷激酶表达增加有关，这与网络兴奋性增加一致。这些数据支持 tau 病理学对 AD 相关癫痫发作的影响，并表明 tau 病理学可能与 Aβ 病理学无关，导致 AD 中癫痫发作的产生。
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