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Open Access 01-12-2018 | Research

Characterisation of tau in the human and rodent enteric nervous system under physiological conditions and in tauopathy

Authors: Arthur Lionnet, Matthew A. Wade, Anne-Gaëlle Corbillé, Alice Prigent, Sébastien Paillusson, Maddalena Tasselli, Jacques Gonzales, Emilie Durieu, Malvyne Rolli-Derkinderen, Emmanuel Coron, Emilie Duchalais, Michel Neunlist, Michael S. Perkinton, Diane P. Hanger, Wendy Noble, Pascal Derkinderen

Published in: Acta Neuropathologica Communications | Issue 1/2018

Abstract

Tau is normally a highly soluble phosphoprotein found predominantly in neurons. Six different isoforms of tau are expressed in the adult human CNS. Under pathological conditions, phosphorylated tau aggregates are a defining feature of neurodegenerative disorders called tauopathies. Recent findings have suggested a potential role of the gut-brain axis in CNS homeostasis, and therefore we set out to examine the isoform profile and phosphorylation state of tau in the enteric nervous system (ENS) under physiological conditions and in tauopathies. Surgical specimens of human colon from controls, Parkinson’s disease (PD) and progressive supranuclear palsy (PSP) patients were analyzed by Western Blot and immunohistochemistry using a panel of anti-tau antibodies. We found that adult human ENS primarily expresses two tau isoforms, localized in the cell bodies and neuronal processes. We did not observe any difference in the enteric tau isoform profile and phosphorylation state between PSP, PD and control subjects. The htau mouse model of tauopathy also expressed two main isoforms of human tau in the ENS, and there were no apparent differences in ENS tau localization or phosphorylation between wild-type and htau mice. Tau in both human and mouse ENS was found to be phosphorylated but poorly susceptible to dephosphorylation with lambda phosphatase. To investigate ENS tau phosphorylation further, primary cultures from rat enteric neurons, which express four isoforms of tau, were pharmacologically manipulated to show that ENS tau phosphorylation state can be regulated, at least in vitro. Our study is the first to characterize tau in the rodent and human ENS. As a whole, our findings provide a basis to unravel the functions of tau in the ENS and to further investigate the possibility of pathological changes in enteric neuropathies and tauopathies.

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Title: Characterisation of tau in the human and rodent enteric nervous system under physiological conditions and in tauopathy
Authors: Arthur Lionnet
Matthew A. Wade
Anne-Gaëlle Corbillé
Alice Prigent
Sébastien Paillusson
Maddalena Tasselli
Jacques Gonzales
Emilie Durieu
Malvyne Rolli-Derkinderen
Emmanuel Coron
Emilie Duchalais
Michel Neunlist
Michael S. Perkinton
Diane P. Hanger
Wendy Noble
Pascal Derkinderen
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Acta Neuropathologica Communications / Issue 1/2018
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-018-0568-3

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Characterisation of tau in the human and rodent enteric nervous system under physiological conditions and in tauopathy

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