Dataset Information

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

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.

SUBMITTER: Lionnet A

PROVIDER: S-EPMC6055332 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Lionnet Arthur A Wade Matthew A MA Corbillé Anne-Gaëlle AG Prigent Alice A Paillusson Sébastien S Tasselli Maddalena M Gonzales Jacques J Durieu Emilie E Rolli-Derkinderen Malvyne M Coron Emmanuel E Duchalais Emilie E Neunlist Michel M Perkinton Michael S MS Hanger Diane P DP Noble Wendy W Derkinderen Pascal P

Acta neuropathologica communications 20180723 1

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) un ...[more]

PMID: 30037345

Similar Datasets

Project description:Alzheimer's disease (AD), the most common tauopathy, is an age-dependent, progressive neurodegenerative disease. Epidemiological studies implicate the role of genetic background in the onset and progression of AD. Despite mutations in familial AD, several risk factors have been implicated in sporadic AD, of which the onset is unknown. In AD, there is a sequential and hierarchical spread of tau pathology to other brain areas. Studies have strived to understand the factors that influence this characteristic spread. Using transgenic rat models with different genetic backgrounds, we reported that the genetic background may influence the manifestation of neurofibrillary pathology. In this study we investigated whether genetic background has an influence in the spread of tau pathology, using hippocampal inoculations of insoluble tau from AD brains in rodent models of tauopathy with either a spontaneously hypertensive (SHR72) or Wistar-Kyoto (WKY72) genetic background. We observed that insoluble tau from human AD induced AT8-positive neurofibrillary structures in the hippocampus of both lines. However, there was no significant difference in the amount of neurofibrillary structures, but the extent of spread was prominent in the W72 line. On the other hand, we observed significantly higher levels of AT8-positive structures in the parietal and frontal cortical areas in W72 when compared to SHR72. Interestingly, we also observed that the microglia in these brain areas in W72 were predominantly phagocytic in morphology (62.4% in parietal and 47.3% in frontal), while in SHR72 the microglia were either reactive or ramified (67.2% in parietal and 84.7% in frontal). The microglia in the hippocampus and occipital cortex in both lines were reactive or ramified structures. Factors such as gender or age are not responsible for the differences observed in these animals. Put together, our results, for the first time, show that the immune response modulating genetic variability is one of the factors that influences the propagation of tau neurofibrillary pathology.

Project description:Piezocrystals, especially the relaxor-based ferroelectric crystals, have been subject to intense investigation and development within the past three decades, motivated by the performance advantages offered by their ultrahigh piezoelectric coefficients and higher electromechanical coupling coefficients than piezoceramics. Structural anisotropy of piezocrystals also provides opportunities for devices to operate in novel vibration modes, such as the d36 face shear mode, with domain engineering and special crystal cuts. These piezocrystal characteristics contribute to their potential usage in a wide range of low- and high-power ultrasound applications. In such applications, conventional piezoelectric materials are presently subject to varying mechanical stress/pressure, temperature and electric field conditions. However, as observed previously, piezocrystal properties are significantly affected by a single such condition or a combination of conditions. Laboratory characterisation of the piezocrystal properties under these conditions is therefore essential to fully understand these materials and to allow electroacoustic transducer design in realistic scenarios. This will help to establish the extent to which these high performance piezocrystals can replace conventional piezoceramics in demanding applications. However, such characterisation requires specific experimental arrangements, examples of which are reported here, along with relevant results. The measurements include high frequency-resolution impedance spectroscopy with the piezocrystal material under mechanical stress 0-60 MPa, temperature 20-200 °C, high electric AC drive and DC bias. A laser Doppler vibrometer and infrared thermal camera are also integrated into the measurement system for vibration mode shape scanning and thermal conditioning with high AC drive. Three generations of piezocrystal have been tested: (I) binary, PMN-PT; (II) ternary, PIN-PMN-PT; and (III) doped ternary, Mn:PIN-PMN-PT. Utilising resonant mode analysis, variations in elastic, dielectric and piezoelectric constants and coupling coefficients have been analysed, and tests with thermal conditioning have been carried out to assess the stability of the piezocrystals under high power conditions.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets