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Title: Early structural and functional defects in synapses and myelinated axons in stratum lacunosum moleculare in two preclinical models for tauopathy
Authors: Maurin, HervĂ© ×
Chong, Seon-Ah
Kraev, Igor
Davies, Heather
Kremer, Anna
Seymour, Claire Marie
Lechat, Benoit
Jaworski, Tomasz
Borghgraef, Peter
Devijver, Herman
Callewaert, Geert
Stewart, Michael G
Van Leuven, Fred #
Issue Date: 2014
Publisher: Public Library of Sciene
Series Title: PLoS One vol:9 issue:2 pages:e87605
Article number: 10.1371/journal.pone.0087605
Abstract: 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.
URI: 
ISSN: 1932-6203
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Experimental Mouse Genetics
Laboratory of Experimental Genetics and Transgenesis (-)
Cellular and Molecular Medicine, Campus Kulak Kortrijk
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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