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Early structural and functional defects in synapses and myelinated axons in stratum lacunosum moleculare in two preclinical models for tauopaty

Maurin, Hervé; 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. and Van Leuven, Fred (2014). Early structural and functional defects in synapses and myelinated axons in stratum lacunosum moleculare in two preclinical models for tauopaty. PLoS ONE

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DOI (Digital Object Identifier) Link: https://doi.org/10.1371/journal.pone.0087605
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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.

Item Type: Journal Item
Copyright Holders: 2014 Maurin et al
ISSN: 1932-6203
Project Funding Details:
Funded Project NameProject IDFunding Body
EUFP7 memstickNot SetNot Set
Keywords: Alzheimer disease; axons; central nervous system; entorhinal cortex; hippocampus; myelin sheath; phosphorylation; synapses
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM)
Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Research Group: Centre for Research in Computing (CRC)
Item ID: 39404
Depositing User: Michael Stewart
Date Deposited: 05 Feb 2014 14:33
Last Modified: 22 May 2019 02:35
URI: http://oro.open.ac.uk/id/eprint/39404
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