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

Arthur Lionnet; Matthew Austen James Wade; Anne-Gaelle Corbille; Alice Prigent; Sebastien Paillusson; Maddalena Tasselli; Jacques Gonzales; Emilie Durieu; Malvyne Derkinderen; Emmanuel Coron; Emilie Duchalais; Michael Neunlist; Michael S. Perkinton; Diane Pamela Hanger; Pascal Derkinderen; Wendy Jane Noble

doi:10.1186/s40478-018-0568-3

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

Arthur Lionnet, Matthew Austen James Wade, Anne-Gaelle Corbille, Alice Prigent, Sebastien Paillusson, Maddalena Tasselli, Jacques Gonzales, Emilie Durieu, Malvyne Derkinderen, Emmanuel Coron, Emilie Duchalais, Michael Neunlist, Michael S. Perkinton, Diane Pamela Hanger, Pascal Derkinderen, Wendy Jane Noble

Basic and Clinical Neuroscience

Research output: Contribution to journal › Article › peer-review

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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 five 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.

Original language	English
Pages (from-to)	1-17
Journal	Acta Neuropathologica Communications
Volume	6
Issue number	1
DOIs	https://doi.org/10.1186/s40478-018-0568-3
Publication status	Published - 24 Jul 2018

Keywords

Tau; tau isoform; tau phosphorylation; enteric nervous system; progressive supranuclear palsy; Parkinson’s disease; gut; biopsy; htau mouse.

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Lionnet, A., Wade, M. A. J., Corbille, A.-G., Prigent, A., Paillusson, S., Tasselli, M., Gonzales, J., Durieu, E., Derkinderen, M., Coron, E., Duchalais, E., Neunlist, M., Perkinton, M. S., Hanger, D. P., Derkinderen, P., & Noble, W. J. (2018). Characterisation of tau in the human and rodent enteric nervous system under physiological conditions and in tauopathy. Acta Neuropathologica Communications, 6(1), 1-17. https://doi.org/10.1186/s40478-018-0568-3

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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{\textquoteright}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 five 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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author = "Arthur Lionnet and Wade, {Matthew Austen James} and Anne-Gaelle Corbille and Alice Prigent and Sebastien Paillusson and Maddalena Tasselli and Jacques Gonzales and Emilie Durieu and Malvyne Derkinderen and Emmanuel Coron and Emilie Duchalais and Michael Neunlist and Perkinton, {Michael S.} and Hanger, {Diane Pamela} and Pascal Derkinderen and Noble, {Wendy Jane}",

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Lionnet, A, Wade, MAJ, Corbille, A-G, Prigent, A, Paillusson, S, Tasselli, M, Gonzales, J, Durieu, E, Derkinderen, M, Coron, E, Duchalais, E, Neunlist, M, Perkinton, MS, Hanger, DP, Derkinderen, P & Noble, WJ 2018, 'Characterisation of tau in the human and rodent enteric nervous system under physiological conditions and in tauopathy', Acta Neuropathologica Communications, vol. 6, no. 1, pp. 1-17. https://doi.org/10.1186/s40478-018-0568-3

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T1 - Characterisation of tau in the human and rodent enteric nervous system under physiological conditions and in tauopathy

AU - Lionnet, Arthur

AU - Wade, Matthew Austen James

AU - Corbille, Anne-Gaelle

AU - Prigent, Alice

AU - Paillusson, Sebastien

AU - Tasselli, Maddalena

AU - Gonzales, Jacques

AU - Durieu, Emilie

AU - Derkinderen, Malvyne

AU - Coron, Emmanuel

AU - Duchalais, Emilie

AU - Neunlist, Michael

AU - Perkinton, Michael S.

AU - Hanger, Diane Pamela

AU - Derkinderen, Pascal

AU - Noble, Wendy Jane

PY - 2018/7/24

Y1 - 2018/7/24

N2 - 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 five 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.

AB - 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 five 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.

KW - Tau; tau isoform; tau phosphorylation; enteric nervous system; progressive supranuclear palsy; Parkinson’s disease; gut; biopsy; htau mouse.

U2 - 10.1186/s40478-018-0568-3

DO - 10.1186/s40478-018-0568-3

M3 - Article

SN - 2051-5960

VL - 6

SP - 1

EP - 17

JO - Acta Neuropathologica Communications

JF - Acta Neuropathologica Communications

IS - 1

ER -

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

Abstract

Keywords

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