Department of Neurology and Regional Epilepsy Center, University of Washington, Seattle, WA, United States.
Department of Neurology and Regional Epilepsy Center, University of Washington, Seattle, WA, United States.
Neuroscience. 2023 Jul 1;522:42-56. doi: 10.1016/j.neuroscience.2023.04.020. Epub 2023 May 2.
Tau is an intracellular protein known to undergo hyperphosphorylation and subsequent neuro-toxic aggregation in Alzheimer's disease (AD). Here, tau expression and phosphorylation at three canonical loci known to be hyperphosphorylated in AD (S202/T205, T181, and T231) were studied in the rat pilocarpine status epilepticus (SE) model of temporal lobe epilepsy (TLE). We measured tau expression at two time points of chronic epilepsy: two months and four months post-SE. Both time points parallel human TLE of at least several years. In the whole hippocampal formation at two months post-SE, we observed modestly reduced total tau levels compared to naïve controls, but no significant reduction in S202/T205 phosphorylation levels. In the whole hippocampal formation from four month post-SE rats, total tau expression had reverted to normal, but there was a significant reduction in S202/T205 tau phosphorylation levels that was also seen in CA1 and CA3. No change in phosphorylation was seen at the T181 and T231 tau loci. In somatosensory cortex, outside of the seizure onset zone, no changes in tau expression or phosphorylation were seen at the later time point. We conclude that total tau expression and phosphorylation in an animal model of TLE do not show hyperphosphorylation at the three AD canonical tau loci. Instead, the S202/T205 locus showed progressive dephosphorylation. This suggests that changes in tau expression may play a different role in epilepsy than in AD. Further study is needed to understand how these changes in tau may impact neuronal excitability in chronic epilepsy.
tau 是一种细胞内蛋白，已知在阿尔茨海默病（AD）中会发生过度磷酸化和随后的神经毒性聚集。在这里，tau 在三个已知在 AD 中过度磷酸化的经典位点（S202/T205、T181 和 T231）的表达和磷酸化在大鼠匹鲁卡品癫痫持续状态（SE）颞叶癫痫（TLE）模型中进行了研究。我们在慢性癫痫的两个时间点测量了 tau 的表达：SE 后两个月和四个月。这两个时间点与人类 TLE 至少几年的时间平行。在 SE 后两个月的整个海马结构中，与未处理的对照相比，我们观察到总 tau 水平略有降低，但 S202/T205 磷酸化水平没有显著降低。在 SE 后四个月的大鼠整个海马结构中，总 tau 表达已恢复正常，但 S202/T205 tau 磷酸化水平显著降低，在 CA1 和 CA3 也可见到。在 T181 和 T231 tau 位点未见磷酸化变化。在躯体感觉皮层，在发作起始区之外，在稍后的时间点未见 tau 表达或磷酸化变化。我们得出结论，TLE 动物模型中的总 tau 表达和磷酸化在三个 AD 经典 tau 位点没有表现出过度磷酸化。相反，S202/T205 位点显示出逐渐去磷酸化。这表明 tau 表达的变化在癫痫中可能发挥与 AD 不同的作用。需要进一步研究以了解 tau 的这些变化如何影响慢性癫痫中的神经元兴奋性。
