Early structural and functional defects in synapses and myelinated axons in stratum lacunosum moleculare in two preclinical models for tauopathy.
The stratum lacunosum moleculare (SLM) is the connection hub between entorhinal cortex and hippocampus, two brain regions that are most vulnerable in Alzheimer's disease. We recently identified a specific synaptic deficit of Nectin-3 in transgenic models for tauopathy. Here we defined cognitive...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3912020?pdf=render |
| _version_ | 1828803247801892864 |
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| author | Hervé Maurin Seon-Ah Chong Igor Kraev Heather Davies Anna Kremer Claire Marie Seymour Benoit Lechat Tomasz Jaworski Peter Borghgraef Herman Devijver Geert Callewaert Michael G Stewart Fred Van Leuven |
| author_facet | Hervé Maurin Seon-Ah Chong Igor Kraev Heather Davies Anna Kremer Claire Marie Seymour Benoit Lechat Tomasz Jaworski Peter Borghgraef Herman Devijver Geert Callewaert Michael G Stewart Fred Van Leuven |
| author_sort | Hervé Maurin |
| collection | DOAJ |
| description | The stratum lacunosum moleculare (SLM) is the connection hub between entorhinal cortex and hippocampus, two brain regions that are most vulnerable in Alzheimer's disease. We recently identified a specific synaptic deficit of Nectin-3 in transgenic models for tauopathy. Here we defined cognitive impairment and electrophysiological problems in the SLM of Tau.P301L mice, which corroborated the structural defects in synapses and dendritic spines. Reduced diffusion of DiI from the ERC to the hippocampus indicated defective myelinated axonal pathways. Ultrastructurally, myelinated axons in the temporoammonic pathway (TA) that connects ERC to CA1 were damaged in Tau.P301L mice at young age. Unexpectedly, the myelin defects were even more severe in bigenic biGT mice that co-express GSK3β with Tau.P301L in neurons. Combined, our data demonstrate that neuronal expression of protein Tau profoundly affected the functional and structural organization of the entorhinal-hippocampal complex, in particular synapses and myelinated axons in the SLM. White matter pathology deserves further attention in patients suffering from tauopathy and Alzheimer's disease. |
| first_indexed | 2024-12-12T07:18:23Z |
| format | Article |
| id | doaj.art-81e57e7a453c43b2be77bb66b288a51e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T07:18:23Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-81e57e7a453c43b2be77bb66b288a51e2022-12-22T00:33:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e8760510.1371/journal.pone.0087605Early structural and functional defects in synapses and myelinated axons in stratum lacunosum moleculare in two preclinical models for tauopathy.Hervé MaurinSeon-Ah ChongIgor KraevHeather DaviesAnna KremerClaire Marie SeymourBenoit LechatTomasz JaworskiPeter BorghgraefHerman DevijverGeert CallewaertMichael G StewartFred Van LeuvenThe stratum lacunosum moleculare (SLM) is the connection hub between entorhinal cortex and hippocampus, two brain regions that are most vulnerable in Alzheimer's disease. We recently identified a specific synaptic deficit of Nectin-3 in transgenic models for tauopathy. Here we defined cognitive impairment and electrophysiological problems in the SLM of Tau.P301L mice, which corroborated the structural defects in synapses and dendritic spines. Reduced diffusion of DiI from the ERC to the hippocampus indicated defective myelinated axonal pathways. Ultrastructurally, myelinated axons in the temporoammonic pathway (TA) that connects ERC to CA1 were damaged in Tau.P301L mice at young age. Unexpectedly, the myelin defects were even more severe in bigenic biGT mice that co-express GSK3β with Tau.P301L in neurons. Combined, our data demonstrate that neuronal expression of protein Tau profoundly affected the functional and structural organization of the entorhinal-hippocampal complex, in particular synapses and myelinated axons in the SLM. White matter pathology deserves further attention in patients suffering from tauopathy and Alzheimer's disease.http://europepmc.org/articles/PMC3912020?pdf=render |
| spellingShingle | Hervé Maurin Seon-Ah Chong Igor Kraev Heather Davies Anna Kremer Claire Marie Seymour Benoit Lechat Tomasz Jaworski Peter Borghgraef Herman Devijver Geert Callewaert Michael G Stewart Fred Van Leuven Early structural and functional defects in synapses and myelinated axons in stratum lacunosum moleculare in two preclinical models for tauopathy. PLoS ONE |
| title | Early structural and functional defects in synapses and myelinated axons in stratum lacunosum moleculare in two preclinical models for tauopathy. |
| title_full | Early structural and functional defects in synapses and myelinated axons in stratum lacunosum moleculare in two preclinical models for tauopathy. |
| title_fullStr | Early structural and functional defects in synapses and myelinated axons in stratum lacunosum moleculare in two preclinical models for tauopathy. |
| title_full_unstemmed | Early structural and functional defects in synapses and myelinated axons in stratum lacunosum moleculare in two preclinical models for tauopathy. |
| title_short | Early structural and functional defects in synapses and myelinated axons in stratum lacunosum moleculare in two preclinical models for tauopathy. |
| title_sort | early structural and functional defects in synapses and myelinated axons in stratum lacunosum moleculare in two preclinical models for tauopathy |
| url | http://europepmc.org/articles/PMC3912020?pdf=render |
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