Neuron-to-neuron wild-type Tau protein transfer through a trans-synaptic mechanism: relevance to sporadic tauopathies.

BACKGROUND: In sporadic Tauopathies, neurofibrillary degeneration (NFD) is characterised by the intraneuronal aggregation of wild-type Tau proteins. In the human brain, the hierarchical pathways of this neurodegeneration have been well established in Alzheimer's disease (AD) and other sporadic tauopathies such as argyrophilic grain disorder and progressive supranuclear palsy but the molecular and cellular mechanisms supporting this progression are yet not known. These pathways appear to be associated with the intercellular transmission of pathology, as recently suggested in Tau transgenic mice. However, these conclusions remain ill-defined due to a lack of toxicity data and difficulties associated with the use of mutant Tau. RESULTS: Using a lentiviral-mediated rat model of hippocampal NFD, we demonstrated that wild-type human Tau protein is axonally transferred from ventral hippocampus neurons to connected secondary neurons even at distant brain areas such as olfactory and limbic systems indicating a trans-synaptic protein transfer. Using different immunological tools to follow phospho-Tau species, it was clear that Tau pathology generated using mutated Tau remains near the IS whereas it spreads much further using the wild-type one. CONCLUSION: Taken together, these results support a novel mechanism for Tau protein transfer compared to previous reports based on transgenic models with mutant cDNA. It also demonstrates that mutant Tau proteins are not suitable for the development of experimental models helpful to validate therapeutic intervention interfering with Tau spreading

Protection of Glial Müller Cells by Dexamethasone in a Mouse Model of Surgically Induced Blood-Retinal Barrier Breakdown.

Purpose: Breakdown of the inner blood-retinal barrier (iBRB) occurs in many retinal disorders and may cause retinal edema often responsible for vision loss. Dexamethasone is used in clinical practice to restore iBRB. The aim of this study was to characterize the impact of a surgically induced iBRB breakdown on retinal homeostatic changes due to dystrophin Dp71, aquaporin-4 (AQP4), and Kir4.1 alterations in Müller glial cells (MGC) in a mouse model. The protective effect of dexamethasone was assessed in this model. Moreover, retinal explants were used to control MGC exposure to a hypoosmotic solution containing barium. Methods: Partial lens surgery was performed in C57BL6/J mice. Dystrophin Dp71, AQP4, and Kir4.1 expression was analyzed by quantitative RT-PCR, Western blot, and immunohistochemistry. Twenty-four hours after surgery, mice received a single intravitreal injection of dexamethasone or of vehicle. Results: After partial lens surgery, iBRB permeability increased while Dp71 and AQP4 were downregulated and Kir4.1 was delocalized. These effects were partially prevented by dexamethasone injection. In the retinal explant model, MGC were swollen and Dp71, AQP4, and Kir4.1 were downregulated after exposure to a hypoosmotic solution containing barium, but not in the presence of dexamethasone. Heat shock factor protein 1 (HSF1) was overexpressed in dexamethasone-treated retinas. Conclusions: Partial lens surgery induces iBRB breakdown and molecular changes in MGC, including a downregulation of Dp71 and AQP4 and the delocalization of Kir4.1. Dexamethasone seems to protect retina from these molecular changes by upregulating HSF1

SNORING: LINEAR STABILITY ANALYSIS ANDIN-VITROEXPERIMENTS

International audienc

Parametric LES/SI Based Aeroacoustic Characterization of Tandem Orifices in Low Mach Number Flows

International audienceAcoustic scattering and noise generation in tandem orifice configurations are examined and modelled. The modelling is carried out by a combination of Large Eddy Simulation (LES) and System Identification (SI). Hereby, an acoustically excited LES is performed. Afterwards, acoustic data series extracted from the LES domain are postprocessed by means of parametric SI methods to concurrently identify both acoustic scattering and noise sources. Adopting a system theory perspective, the scattering matrix is represented by the so-called "plant model" whereas the noise sources are described using a "noise model". Here, two tandem orifice configurations are investigated to assess the influence of the distance between the two singularities on the acoustic power produced by the whole system. The acoustic power generated or dissipated across the double orifices is evaluated by means of the socalled whistling criterion. Hereby, the whistling potentiality of the two tandem orifice configurations is computed from the identified scattering matrix. The deduced acoustic power is subsequently compared against the whistling potentiality of one single orifice composing the ducted systems to evince the influence of the distance between the singularities. Numerical results are validated against experimental data measured for the same geometries and for the same flow

Ten years follow-up after surgery for a foveal detachment due to optic disc pit: a case report of outer retinal layer healing

Abstract Background To report a case of complete progressive visual recovery and healing of outer retinal layers after vitrectomy for foveal detachment associated with optic disc pit. Case presentation Optical coherence tomography (OCT) follow-up was performed on a 15-year-old boy with deep optic disc pit and foveal detachment, before and for 10 years after vitrectomy with gas. The foveal detachment was successfully reattached with complete reapplication of the retina. OCT scans showed a progressive long-term retinal healing with reappearance of the ellipsoid line and visual acuity improved from 20/100 before surgery to 20/25, 10 years after surgery. Conclusions Photoreceptor regeneration after foveal detachment surgery has been already described only in zebrafish but never humans. However, we highlight with this case that in humans, a healing process of the outer retinal layers can occur with reappearance of the ellipsoid zone on OCT. This healing process may take several years and allow a complete functional restoration