Impaired plasticity of cortical dendritic spines in P301S tau transgenic mice

Acta Neuropathologica Communications
Nadine A HoffmannJochen Herms

Abstract

Illuminating the role of the microtubule-associated protein tau in neurodegenerative diseases is of increasing importance, supported by recent studies establishing novel functions of tau in synaptic signalling and cytoskeletal organization. In severe dementias like Alzheimer's disease (AD), synaptic failure and cognitive decline correlate best with the grade of tau-pathology. To address synaptic alterations in tauopathies, we analyzed the effects of mutant tau expression on excitatory postsynapses in vivo. Here we followed the fate of single dendritic spines in the neocortex of a tauopathy mouse model, expressing human P301S mutated tau, for a period of two weeks. We observed a continuous decrease in spine density during disease progression, which we could ascribe to a diminished fraction of gained spines. Remaining spines were enlarged and elongated, thus providing evidence for morphological reorganization in compensation for synaptic dysfunction. Remarkably, loss of dendritic spines in cortical pyramidal neurons occurred in the absence of neurofibrillary tangles (NFTs). Therefore, we consider prefibrillar tau species as causative for the observed impairment in spine plasticity. Dendritic spine plasticity and morphology are al...Continue Reading

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Citations

Nov 30, 2014·Molecular Neurodegeneration·Odochi Ohia-NwokoJason L Eriksen
Jun 13, 2015·Acta Neuropathologica·Mario M DorostkarJochen Herms
Dec 11, 2014·Acta Neuropathologica·Rebecca M NisbetJürgen Götz
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Jul 19, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Pei-Pei Guan, Pu Wang
Mar 9, 2019·Brain : a Journal of Neurology·Petar MarinkovićJochen Herms
Jan 13, 2015·Medicine and Science in Sports and Exercise·Jinkyung ChoHyunsik Kang
Aug 20, 2020·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Courtney K Walker, Jeremy H Herskowitz
Oct 23, 2015·Translational Neuroscience·Santosh JadhavNorbert Zilka
Jun 17, 2020·The Journal of Clinical Investigation·Maud GratuzeDavid M Holtzman
Dec 26, 2018·Journal of Alzheimer's Disease : JAD·Charisse N WinstonShauna H Yuan
Dec 10, 2019·Acta Neuropathologica Communications·Enrico FaldiniDetlef Balschun
Feb 3, 2021·Brain : a Journal of Neurology·Iain J HartnellDelphine Boche
Jan 8, 2021·Frontiers in Cellular Neuroscience·Jaichandar SubramanianMarie-Ève Tremblay
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Nov 17, 2020·Frontiers in Cellular Neuroscience·Chang Geon ChungSung Bae Lee
May 21, 2020·Cerebral Cortex Communications·Mamen Regalado-ReyesGonzalo León-Espinosa

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Methods Mentioned

BETA
transgenic
PCR

Software Mentioned

Prism
AutoQuant
Imaris XT
Adobe Illustrator CS4
Imaris
ZEN 2011 Light Edition
ZEN
GraphPad

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