Oligodendrogenesis increases in hippocampal grey and white matter prior to locomotor or memory impairment in an adult mouse model of tauopathy.
Oligodendrogenesis increases in hippocampal grey and white matter prior to locomotor or memory impairment in an adult mouse model of tauopathy.
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DOI：
10.1111/ejn.14726
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Cullen CL
中科院分区：
文献类型：
--
作者：
Ferreira S;Pitman KA;Summers BS;Wang S;Young KM;Cullen CL
髓鞘和轴突损失与健康老龄化中的认知能力下降有关，但在被诊断患有tau蛋白病的人中情况更糟。为了确定tau蛋白病是否也与髓鞘可塑性增强有关，我们评估了表达微管相关蛋白tau（MAPTP301S）的人类病理变体的小鼠中OPCs的行为。到6个月大时（P180），MAPTP301S小鼠过度表达过度磷酸化tau蛋白，并在海马中发生反应性胶质增生，但未发生明显的运动或记忆障碍。通过对成年OPCs进行cre‐lox谱系追踪，我们确定了在P150之前，对照组和MAPTP301S小鼠中添加到海马、内嗅皮质和海马伞的新生少突胶质细胞的数量相等。然而，在P150和P180之间，在MAPTP301S小鼠脑中的这些区域中添加了显著更多的新少突胶质细胞。这种新的少突胶质细胞数量的大量增加不是OPC增殖增加的结果，也没有改变海马、内嗅皮质或海马伞中的少突胶质细胞密度，这在P180野生型和MAPTP301S小鼠中是等同的。此外，海马和海马伞轴突与髓鞘的比例不受tau蛋白病的影响。然而，与野生型同窝小鼠相比，P180 MAPTP301S小鼠海马和海马伞中未成熟髓鞘节间包裹的有髓鞘轴突比例显著增加。这些数据表明MAPTP301S转基因小鼠经历显著的少突胶质细胞更新，新生少突胶质细胞在tau蛋白病发展早期补偿髓鞘损失。过表达人类微管相关蛋白tau（MAPT P301S）的病理变体的小鼠在5至6个月龄之间经历海马、内嗅皮质和海马伞中少突神经生成增加。总少突胶质细胞和少突胶质细胞祖细胞数量、轴突密度和有髓鞘轴突的百分比保持正常，尽管新生成的髓鞘增加，表明少突胶质细胞更新发生在tau蛋白病发展的早期。
Myelin and axon losses are associated with cognitive decline in healthy ageing but are worse in people diagnosed with tauopathy. To determine whether tauopathy is also associated with enhanced myelin plasticity, we evaluated the behaviour of OPCs in mice that expressed a human pathological variant of microtubule‐associated protein tau (MAPTP301S ). By 6 months of age (P180), MAPTP301S mice overexpressed hyperphosphorylated tau and had developed reactive gliosis in the hippocampus but had not developed overt locomotor or memory impairment. By performing cre‐lox lineage tracing of adult OPCs, we determined that the number of newborn oligodendrocytes added to the hippocampus, entorhinal cortex and fimbria was equivalent in control and MAPTP301S mice prior to P150. However, between P150 and P180, significantly more new oligodendrocytes were added to these regions in the MAPTP301S mouse brain. This large increase in new oligodendrocyte number was not the result of increased OPC proliferation, nor did it alter oligodendrocyte density in the hippocampus, entorhinal cortex or fimbria, which was equivalent in P180 wild‐type and MAPTP301S mice. Furthermore, the proportion of hippocampal and fimbria axons with myelin was unaffected by tauopathy. However, the proportion of myelinated axons that were ensheathed by immature myelin internodes was significantly increased in the hippocampus and fimbria of P180 MAPTP301S mice, when compared with their wild‐type littermates. These data suggest that MAPTP301S transgenic mice experience significant oligodendrocyte turnover, with newborn oligodendrocytes compensating for myelin loss early in the development of tauopathy. Mice overexpressing a pathological variant of human microtubule‐associated protein tau (MAPT P301S) experience increased oligodendrogenesis in the hippocampus, entorhinal cortex and fimbria between 5 and 6 months of age. Total oligodendrocyte and oligodendrocyte progenitor cell number, axon density and the per cent of myelinated axons remain normal, though there is an increase in newly generated myelin, suggesting that oligodendrocyte turnover occurs early in the development of tauopathy.
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影响因子：
17.1
作者：
Fard MK;van der Meer F;Sánchez P;Cantuti-Castelvetri L;Mandad S;Jäkel S;Fornasiero EF;Schmitt S;Ehrlich M;Starost L;Kuhlmann T;Sergiou C;Schultz V;Wrzos C;Brück W;Urlaub H;Dimou L;Stadelmann C;Simons M
通讯作者：
Simons M
影响因子：
6.2
作者：
Baxi EG;DeBruin J;Jin J;Strasburger HJ;Smith MD;Orthmann-Murphy JL;Schott JT;Fairchild AN;Bergles DE;Calabresi PA
通讯作者：
Calabresi PA
影响因子：
6
作者：
Desai, Maya K.;Mastrangelo, Michael A.;Bowers, William J.
通讯作者：
Bowers, William J.
影响因子：
3.7
作者：
Attar A;Liu T;Chan WT;Hayes J;Nejad M;Lei K;Bitan G
通讯作者：
Bitan G
影响因子：
4.8
作者：
Ferrer, Isidro;Aguilo Garcia, Meritxell;Antonio del Rio, Jose
通讯作者：
Antonio del Rio, Jose