Tau expression and phosphorylation in enteroendocrine cells

Background and objectiveThere is mounting evidence to suggest that the gut-brain axis is involved in the development of Parkinson’s disease (PD). In this regard, the enteroendocrine cells (EEC), which faces the gut lumen and are connected with both enteric neurons and glial cells have received growing attention. The recent observation showing that these cells express alpha-synuclein, a presynaptic neuronal protein genetically and neuropathologically linked to PD came to reinforce the assumption that EEC might be a key component of the neural circuit between the gut lumen and the brain for the bottom-up propagation of PD pathology. Besides alpha-synuclein, tau is another key protein involved in neurodegeneration and converging evidences indicate that there is an interplay between these two proteins at both molecular and pathological levels. There are no existing studies on tau in EEC and therefore we set out to examine the isoform profile and phosphorylation state of tau in these cells.MethodsSurgical specimens of human colon from control subjects were analyzed by immunohistochemistry using a panel of anti-tau antibodies together with chromogranin A and Glucagon-like peptide-1 (two EEC markers) antibodies. To investigate tau expression further, two EEC lines, namely GLUTag and NCI-H716 were analyzed by Western blot with pan-tau and tau isoform specific antibodies and by RT-PCR. Lambda phosphatase treatment was used to study tau phosphorylation in both cell lines. Eventually, GLUTag were treated with propionate and butyrate, two short chain fatty acids known to sense EEC, and analyzed at different time points by Western blot with an antibody specific for tau phosphorylated at Thr205.ResultsWe found that tau is expressed and phosphorylated in EEC in adult human colon and that both EEC lines mainly express two tau isoforms that are phosphorylated under basal condition. Both propionate and butyrate regulated tau phosphorylation state by decreasing its phosphorylation at Thr205.Conclusion and inferenceOur study is the first to characterize tau in human EEC and in EEC lines. As a whole, our findings provide a basis to unravel the functions of tau in EEC and to further investigate the possibility of pathological changes in tauopathies and synucleinopathies

CpG-ODN and MPLA Prevent Mortality in a Murine Model of Post-Hemorrhage-Staphyloccocus aureus Pneumonia

Infections are the most frequent cause of complications in trauma patients. Post-traumatic immune suppression (IS) exposes patients to pneumonia (PN). The main pathogen involved in PN is Methicillin Susceptible Staphylococcus aureus (MSSA). Dendritic cells () may be centrally involved in the IS. We assessed the consequences of hemorrhage on pneumonia outcomes and investigated its consequences on DCs functions. A murine model of hemorrhagic shock with a subsequent MSSA pneumonia was used. Hemorrhage decreased the survival rate of infected mice, increased systemic dissemination of sepsis and worsened inflammatory lung lesions. The mRNA expression of Tumor Necrosis Factor-alpha (TNF-α), Interferon-beta (IFN-β) and Interleukin (IL)-12p40 were mitigated for hemorrhaged-mice. The effects of hemorrhage on subsequent PN were apparent on the pDCs phenotype (reduced MHC class II, CD80, and CD86 molecule membrane expression). In addition, hemorrhage dramatically decreased CD8+ cDCs- and CD8- cDCs-induced allogeneic T-cell proliferation during PN compared with mice that did not undergo hemorrhage. In conclusion, hemorrhage increased morbidity and mortality associated with PN; induced severe phenotypic disturbances of the pDCs subset and functional alterations of the cDCs subset. After hemorrhage, a preventive treatment with CpG-ODN or Monophosphoryl Lipid A increased transcriptional activity in DCs (TNF-α, IFN-β and IL-12p40) and decreased mortality of post-hemorrhage MSSA pneumonia

Expression du transporteur des monocarboxylates MCT1 dans le côlon sain et pathologique

NANTES-BU Sciences (441092104) / SudocSudocFranceF

Duodenal fatty acid sensing is not altered by perinatal malnutrition in adult rat born with intrauterine growth retardation

Duodenal fatty acid sensing is not altered by perinatal malnutrition in adult rat born with intrauterine growth retardation. 3eme congrès SF DOHaD 201

Rôle du stress du réticulum endoplasmique dans les modifications épigénétiques associées aux altérations de la barrière épithéliale colique

Rôle du stress du réticulum endoplasmique dans les modifications épigénétiques associées aux altérations de la barrière épithéliale colique. 34. Réunion annuelle du Club d'Etudes des Cellules Epithéliales Digestives (CECED

Butyrate utilization by the colonic mucosa in inflammatory bowel diseases : A transport deficiency

The short-chain fatty acid butyrate, which is mainly produced in the lumen of the large intestine by the fermentation of dietary fibers, plays a major role in the physiology of the colonic mucosa. It is also the major energy source for the colonocyte. Numerous studies have reported that butyrate metabolism is impaired in intestinal inflamed mucosa of patients with inflammatory bowel disease (IBD). The data of butyrate oxidation in normal and inflamed colonic tissues depend on several factors, such as the methodology or the models used or the intensity of inflammation. The putative mechanisms involved in butyrate oxidation impairment may include a defect in beta oxidation, luminal compounds interfering with butyrate metabolism, changes in luminal butyrate concentrations or pH, and a defect in butyrate transport. Recent data show that butyrate deficiency results from the reduction of butyrate uptake by the inflamed mucosa through downregulation of the monocarboxylate transporter MCT1. The concomitant induction of the glucose transporter GLUT1 suggests that inflammation could induce a metabolic switch from butyrate to glucose oxidation. Butyrate transport deficiency is expected to have clinical consequences. Particularly, the reduction of the intracellular availability of butyrate in colonocytes may decrease its protective effects toward cancer in IBD patients

Is perinatal butyrate, through maternal supplementation, able to prevent cognitive impairment due to intrauterine growth restriction in a rat model ?

International audienc

Impact du retard de croissance intra-utérin sur l'hépithélium colique

Impact du retard de croissance intra-utérin sur l'hépithélium colique. 34. Réunion annuelle du Club d'Etudes des Cellules Epithéliales Digestives (CECED

Une dénutrition protéique foetale altère à long terme la barrière épithéliale colique

Une dénutrition protéique foetale altère à long terme la barrière épithéliale colique. 34. Réunion annuelle du Club d'Etudes des Cellules Epithéliales Digestives (CECED

Intrauterine growth retardation induces alterations of colonic epithelial barrier and increases the risk of colonic diseases in adult rats.

Intrauterine growth retardation induces alterations of colonic epithelial barrier and increases the risk of colonic diseases in adult rats.. Colloque fondateur de la SF-DOHa