The Curious Anti-Pathology of the Wlds Mutation: Paradoxical Postsynaptic Spine Growth Accompanies Delayed Presynaptic Wallerian Degeneration
The Wlds 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...
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2021.735919/full |
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| author | Oswald Steward Oswald Steward Oswald Steward Oswald Steward Oswald Steward Jennifer M. Yonan Jennifer M. Yonan Paula M. Falk |
| author_facet | Oswald Steward Oswald Steward Oswald Steward Oswald Steward Oswald Steward Jennifer M. Yonan Jennifer M. Yonan Paula M. Falk |
| author_sort | Oswald Steward |
| collection | DOAJ |
| description | The Wlds 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 Wlds 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 Wlds 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 Wlds 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. |
| first_indexed | 2024-12-16T14:40:55Z |
| format | Article |
| id | doaj.art-e59b4793677a484190619a34bc0e0a2e |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-16T14:40:55Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-e59b4793677a484190619a34bc0e0a2e2022-12-21T22:27:57ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992021-09-011410.3389/fnmol.2021.735919735919The Curious Anti-Pathology of the Wlds Mutation: Paradoxical Postsynaptic Spine Growth Accompanies Delayed Presynaptic Wallerian DegenerationOswald Steward0Oswald Steward1Oswald Steward2Oswald Steward3Oswald Steward4Jennifer M. Yonan5Jennifer M. Yonan6Paula M. Falk7Reeve-Irvine Research Center, University of California, Irvine, Irvine, CA, United StatesDepartment of Anatomy & Neurobiology, University of California, Irvine, Irvine, CA, United StatesDepartment of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, United StatesDepartment of Neurosurgery, University of California, Irvine, Irvine, CA, United StatesDepartment of Neuroscience, University of Virginia, Charlottesville, VA, United StatesReeve-Irvine Research Center, University of California, Irvine, Irvine, CA, United StatesDepartment of Anatomy & Neurobiology, University of California, Irvine, Irvine, CA, United StatesDepartment of Neuroscience, University of Virginia, Charlottesville, VA, United StatesThe Wlds 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 Wlds 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 Wlds 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 Wlds 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.https://www.frontiersin.org/articles/10.3389/fnmol.2021.735919/fullnicotinamide adenyltransferase 1 (NMNAT1)ubiquitination factor U4Bdenervationreinnervationdentate gyrusentorhinal cortex |
| spellingShingle | Oswald Steward Oswald Steward Oswald Steward Oswald Steward Oswald Steward Jennifer M. Yonan Jennifer M. Yonan Paula M. Falk The Curious Anti-Pathology of the Wlds Mutation: Paradoxical Postsynaptic Spine Growth Accompanies Delayed Presynaptic Wallerian Degeneration Frontiers in Molecular Neuroscience nicotinamide adenyltransferase 1 (NMNAT1) ubiquitination factor U4B denervation reinnervation dentate gyrus entorhinal cortex |
| title | The Curious Anti-Pathology of the Wlds Mutation: Paradoxical Postsynaptic Spine Growth Accompanies Delayed Presynaptic Wallerian Degeneration |
| title_full | The Curious Anti-Pathology of the Wlds Mutation: Paradoxical Postsynaptic Spine Growth Accompanies Delayed Presynaptic Wallerian Degeneration |
| title_fullStr | The Curious Anti-Pathology of the Wlds Mutation: Paradoxical Postsynaptic Spine Growth Accompanies Delayed Presynaptic Wallerian Degeneration |
| title_full_unstemmed | The Curious Anti-Pathology of the Wlds Mutation: Paradoxical Postsynaptic Spine Growth Accompanies Delayed Presynaptic Wallerian Degeneration |
| title_short | The Curious Anti-Pathology of the Wlds Mutation: Paradoxical Postsynaptic Spine Growth Accompanies Delayed Presynaptic Wallerian Degeneration |
| title_sort | curious anti pathology of the wlds mutation paradoxical postsynaptic spine growth accompanies delayed presynaptic wallerian degeneration |
| topic | nicotinamide adenyltransferase 1 (NMNAT1) ubiquitination factor U4B denervation reinnervation dentate gyrus entorhinal cortex |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2021.735919/full |
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