Biology subjects

Barthelemy, A.

Publications and source records attributed to Barthelemy, A..

2 recordsLinked to original sources

bioRxiv2022

Release of VAMP5-positive extracellular vesicles from specialized domains of retinal Müller cells in vivo

Cell-cell interactions in the central nervous system are based on the release of molecules mediating signal exchange and providing structural and trophic support through vesicular exocytosis and the formation of extracellular vesicles. The specific mechanisms employed by each cell type in the brain are incompletely understood. Here, we explored the means of communication used by Muller cells, a type of radial glial cells in the retina, which forms part of the central nervous system. Using immunohistochemical, electron microscopic, and molecular analyses, we provide evidence for the release of distinct extracellular vesicles from endfeet and microvilli of retinal Muller cells in adult mice in vivo. We identify VAMP5 as a Muller cell-specific SNARE component that is part of extracellular vesicles and responsive to ischemia, and we reveal differences between the secretomes of immunoaffinity-purified Muller cells and neurons in vitro. Our findings suggest extracellular vesicle-based communication as an important mediator of cellular interactions in the retina.

neuroscience↗

bioRxiv2021

Glial contribution to cyclodextrin-mediated reversal of cholesterol accumulation in murine NPC1-deficient neurons in vivo

Niemann-Pick type C (NPC) disease is a rare and fatal lysosomal storage disorder presenting severe neurovisceral symptoms. Disease-causing mutations in genes encoding either NPC1 or NPC2 protein provoke accumulation of cholesterol and other lipids in specific structures of the endosomal-lysosomal system and degeneration of specific cells, notably neurons in the central nervous system (CNS). 2-hydroxypropyl-beta-cyclodextrin (CD) emerged as potential therapeutic approach based on animal studies and clinical data, but the mechanism of action on neurons has remained unclear. To address this topic in vivo, we took advantage of the retina as highly accessible part of the (CNS) and intravitreal injections as mode of drug administration. We find that CD enters the endosomal-lysosomal system of neurons and enables the release of lipid-laden lamellar inclusions, which are then removed from the extracellular space by specific types of glial cells. Thus, CD triggers a concerted action of neurons and glial cells to restore lipid homeostasis in the central nervous system.

neuroscience↗