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首页> 美国卫生研究院文献>Frontiers in Neuroscience >Extended Postnatal Brain Development in the Longest-Lived Rodent: Prolonged Maintenance of Neotenous Traits in the Naked Mole-Rat Brain
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Extended Postnatal Brain Development in the Longest-Lived Rodent: Prolonged Maintenance of Neotenous Traits in the Naked Mole-Rat Brain

机译：寿命最长的啮齿动物的产后脑扩展发育：裸鼠痣大脑中近代性状的长期维持

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The naked mole-rat (NMR) is the longest-lived rodent with a maximum lifespan >31 years. Intriguingly, fully-grown naked mole-rats (NMRs) exhibit many traits typical of neonatal rodents. However, little is known about NMR growth and maturation, and we question whether sustained neotenous features when compared to mice, reflect an extended developmental period, commensurate with their exceptionally long life. We tracked development from birth to 3 years of age in the slowest maturing organ, the brain, by measuring mass, neural stem cell proliferation, axonal, and dendritic maturation, synaptogenesis and myelination. NMR brain maturation was compared to data from similar sized rodents, mice, and to that of long-lived mammals, humans, and non-human primates. We found that at birth, NMR brains are significantly more developed than mice, and rather are more similar to those of newborn primates, with clearly laminated hippocampi and myelinated white matter tracts. Despite this more mature brain at birth than mice, postnatal NMR brain maturation occurs at a far slower rate than mice, taking four-times longer than required for mice to fully complete brain development. At 4 months of age, NMR brains reach 90% of adult size with stable neuronal cytostructural protein expression whereas myelin protein expression does not plateau until 9 months of age in NMRs, and synaptic protein expression continues to change throughout the first 3 years of life. Intriguingly, NMR axonal composition is more similar to humans than mice whereby NMRs maintain expression of three-repeat (3R) tau even after brain growth is complete; mice experience an abrupt downregulation of 3R tau by postnatal day 8 which continues to diminish through 6 weeks of age. We have identified key ages in NMR cerebral development and suggest that the long-lived NMR may provide neurobiologists an exceptional model to study brain developmental processes that are compressed in common short-lived laboratory animal models.
机译：裸鼠（NMR）是寿命最长的啮齿动物，最大寿命> 31年。有趣的是，成熟的裸鼠（NMR）具有许多新生啮齿类动物的特征。然而，人们对NMR的生长和成熟知之甚少，我们质疑与小鼠相比，持续的新生特征是否反映出延长的发育时期，与它们的超长寿命相称。通过测量质量，神经干细胞增殖，轴突和树突成熟，突触形成和髓鞘形成，我们追踪了最慢的成熟器官大脑中从出生到3岁的发育情况。将NMR脑成熟与类似大小的啮齿动物，小鼠以及长寿哺乳动物，人类和非人类灵长类动物的数据进行了比较。我们发现，在出生时，NMR脑比小鼠显着发达，并且与新生灵长类动物更为相似，具有清晰的层压海马体和髓鞘白质束。尽管出生时的大脑比小鼠更成熟，但是出生后NMR大脑的成熟速度却比小鼠慢得多，比完全完成大脑发育所需的时间长四倍。在4个月大时，NMR脑达到成人大小的90％，具有稳定的神经元细胞结构蛋白表达，而髓磷脂蛋白的表达直到9个月大时才稳定，并且在生命的前3年中突触蛋白的表达持续变化。有趣的是，NMR轴突的成分与人类比小鼠更相似，因此即使在大脑发育完全后，NMR仍能维持三重复（3R）tau的表达。小鼠在出生后第8天经历3R tau的突然下调，并在6周龄后持续下降。我们已经确定了NMR脑发育的关键年龄，并认为长寿命NMR可能为神经生物学家提供一种特殊的模型，用于研究在普通的短寿命实验动物模型中受压的大脑发育过程。

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