Altered Synapse Stability in the Early Stages of Tauopathy.
Altered Synapse Stability in the Early Stages of Tauopathy.
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DOI：
10.1016/j.celrep.2017.03.013
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发表时间：
2017-03-28
期刊：
影响因子：
8.8
通讯作者：
Ashby MC
中科院分区：
文献类型：
--
作者：
Jackson JS;Witton J;Johnson JD;Ahmed Z;Ward M;Randall AD;Hutton ML;Isaac JT;O'Neill MJ;Ashby MC
突触丧失是痴呆症的一个关键特征，但尚不清楚突触功能障碍是否先于疾病的退行性阶段。在这里，我们表明，即使在突触密度的任何减少，有异常营业额的皮质轴突终扣和树突棘在小鼠模型的tau蛋白病相关的痴呆症。引人注目的是，tau蛋白病导致突触转换的不匹配;突触后棘翻转得更快，而突触前终扣稳定。突触前和突触后稳定性之间的这种不平衡与疾病的退行性前阶段中突触驱动的神经元活动减少相一致。皮质轴突终扣和树突棘的密度在tau蛋白病中早期降低。在突触密度降低之前，存在突触稳定性和大小的异常。树突棘的转换率升高，而突触前终扣稳定。发现突触稳定性在tau蛋白病的前退行性阶段改变。突触前和突触后转换的不匹配异常与神经元活动中断一致。
Synapse loss is a key feature of dementia, but it is unclear whether synaptic dysfunction precedes degenerative phases of the disease. Here, we show that even before any decrease in synapse density, there is abnormal turnover of cortical axonal boutons and dendritic spines in a mouse model of tauopathy-associated dementia. Strikingly, tauopathy drives a mismatch in synapse turnover; postsynaptic spines turn over more rapidly, whereas presynaptic boutons are stabilized. This imbalance between pre- and post-synaptic stability coincides with reduced synaptically driven neuronal activity in pre-degenerative stages of the disease. Density of cortical axonal boutons and dendritic spines is reduced early in tauopathy Abnormalities in synaptic stability and size exist before decreases in synapse density Turnover of dendritic spines is elevated, whereas presynaptic boutons are stabilized Neuronal activity is reduced at stages associated with mismatched synaptic turnover Using in vivo two-photon imaging in the rTg4510 tauopathy mouse model, Jackson et al. find that synapse stability is altered during the pre-degenerative stages of tauopathy. Mismatched abnormalities in pre- and post-synaptic turnover coincide with disrupted neuronal activity.