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The Curious Anti-Pathology of the Wld s Mutation: Paradoxical Postsynaptic Spine Growth Accompanies Delayed Presynaptic Wallerian Degeneration.
Frontiers in Molecular Neuroscience ( IF 3.5 ) Pub Date : 2021-09-10 , DOI: 10.3389/fnmol.2021.735919
Oswald Steward 1, 2, 3, 4, 5 , Jennifer M Yonan 1, 2 , Paula M Falk 5
Affiliation  

The Wld s mutation, which arose spontaneously in C57Bl/6 mice, remarkably delays the onset of Wallerian degeneration of axons. This remarkable phenotype has transformed our understanding of mechanisms contributing to survival vs. degeneration of mammalian axons after separation from their cell bodies. Although there are numerous studies of how the Wld s mutation affects axon degeneration, especially in the peripheral nervous system, less is known about how the mutation affects degeneration of CNS synapses. Here, using electron microscopy, we explore how the Wld s mutation affects synaptic terminal degeneration and withering and re-growth of dendritic spines on dentate granule cells following lesions of perforant path inputs from the entorhinal cortex. Our results reveal that substantial delays in the timing of synapse degeneration in Wld s mice are accompanied by paradoxical hypertrophy of spine heads with enlargement of post-synaptic membrane specializations (PSDs) and development of spinules. These increases in the complexity of spine morphology are similar to what is seen following induction of long-term potentiation (LTP). Robust and paradoxical spine growth suggests yet to be characterized signaling processes between amputated but non-degenerating axons and their postsynaptic targets.

中文翻译:

Wld 突变的奇怪抗病理学:矛盾的突触后脊柱生长伴随着延迟的突触前沃勒变性。

Wld s 突变在 C57Bl/6 小鼠中自发出现,显着延迟了轴突沃勒变性的发生。这种非凡的表型改变了我们对哺乳动物轴突从细胞体分离后存活与退化的机制的理解。尽管有大量关于 Wld 突变如何影响轴突退化的研究,特别是在周围神经系统中,但对突变如何影响 CNS 突触退化的了解较少。在这里,我们使用电子显微镜研究了 Wld 突变如何影响突触末端变性以及在来自内嗅皮层的穿孔通路输入损伤后齿状颗粒细胞上树突棘的枯萎和再生长。我们的研究结果表明,Wld 小鼠突触变性时间的显着延迟伴随着脊柱头部的矛盾性肥大,突触后膜特化(PSDs)的扩大和小刺的发育。这些脊柱形态复杂性的增加类似于诱导长时程增强 (LTP) 后所见。健壮和矛盾的脊柱生长表明截肢但非退化的轴突与其突触后目标之间的信号过程尚待表征。
更新日期:2021-09-10
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