Tau Phosphorylation-Associated Spine Regression Does Not Impair Hippocampal-Dependent Memory in Hibernating Golden Hamsters
Tau Phosphorylation-Associated Spine Regression Does Not Impair Hippocampal-Dependent Memory in Hibernating Golden Hamsters
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DOI：
10.1002/hipo.22522
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发表时间：
2016-03-01
期刊：
影响因子：
3.5
通讯作者：
Arendt, Thomas
中科院分区：
文献类型：
--
作者：
Bullmann, Torsten;Seeger, Gudrun;Arendt, Thomas
过度磷酸化形式的微管相关蛋白 tau 是神经退行性疾病（通常称为“tau蛋白病”）中成对螺旋丝和其他聚集体的主要成分。然而，最近的证据表明，过度磷酸化的 tau 蛋白错误定位到突触下位点，甚至早在 tau 蛋白聚集体形成和神经退行性疾病发生之前就会导致突触损伤和认知能力下降。在冬眠期间的生理控制条件下，tau 蛋白也会发生类似但可逆的过度磷酸化。在这里，我们研究冬眠的金仓鼠（叙利亚仓鼠，Mesocricetus auratus）。在海马中观察到短暂的脊柱减少，特别是在海马 CA3 锥体细胞的顶端树突上，但在其基底树突上没有。结构突触回归的这种分布与磷酸化 tau 蛋白的分布相关，磷酸化 tau 蛋白在顶端树突中含量很高，但在基底树突中几乎检测不到。令人惊讶的是，通过迷宫评估的海马记忆并未受到冬眠的影响。本研究表明可溶性过度磷酸化 tau 在可逆突触退化过程中发挥作用，这不会导致冬眠期间的记忆障碍。我们假设 tau 磷酸化相关的脊柱退化可能主要影响不稳定/动态的脊柱，同时不影响已建立的/稳定的脊柱。 (C) 2015Wiley 期刊公司。
The microtubule-associated protein tau, in its hyperphosphorylated form, is the major component of paired helical filaments and other aggregates in neurodegenerative disorders commonly referred to as "tauopathies". Recent evidence, however, indicates that mislocalization of hyperphosphorylated tau to subsynaptic sites leads to synaptic impairment and cognitive decline even long before formation of tau aggregates and neurodegeneration occur. A similar, but reversible hyperphosphorylation of tau occurs under physiologically controlled conditions during hibernation. Here, we study the hibernating Golden hamster (Syrian hamster, Mesocricetus auratus). A transient spine reduction was observed in the hippocampus, especially on apical dendrites of hippocampal CA3 pyramidal cells, but not on their basal dendrites. This distribution of structural synaptic regression was correlated to the distribution of phosphorylated tau, which was highly abundant in apical dendrites but hardly detectable in basal dendrites. Surprisingly, hippocampal memory assessed by a labyrinth maze was not affected by hibernation. The present study suggests a role for soluble hyperphosphorylated tau in the process of reversible synaptic regression, which does not lead to memory impairment during hibernation. We hypothesize that tau phosphorylation associated spine regression might mainly affect unstable/dynamic spines while sparing established/stable spines. (C) 2015Wiley Periodicals, Inc.