Contributors: Signalisation et Transports Ioniques Membranaires (STIM Poitiers ); Université de Poitiers = University of Poitiers (UP)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS); Sechenov Institute of Evolutionary Physiology and Biochemistry; Russian Academy of Sciences Moscow (RAS); Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou; ImageUP (Plateforme d'Imagerie de l'Université de Poitiers); Université de Poitiers = University of Poitiers (UP); Biosit : biologie, santé, innovation technologique (SFR UMS CNRS 3480 - INSERM 018); Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes (Biosit : Biologie - Santé - Innovation Technologique); Centre de Microscopie de Rennes (MRic); Université de Rennes (UR)-Structure Fédérative de Recherche en Biologie et Santé de Rennes (Biosit : Biologie - Santé - Innovation Technologique); Laboratoire de neurosciences cognitives et adaptatives (LNCA); Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS); Institut de recherche en santé, environnement et travail (Irset); Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique EHESP (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes (Biosit : Biologie - Santé - Innovation Technologique); Centre hospitalier universitaire de Poitiers = Poitiers University Hospital (CHU de Poitiers La Milétrie ); Agence Nationale de la Recherche, ANR: ANR-2017-CE12-0027; Institut National de la Santé et de la Recherche Médicale, Inserm: U1085; Centre National de la Recherche Scientifique, CNRS; ANR-17-CE12-0027,EpiHD,Rôle des mécanismes épigénétiques dans la maladie de Huntington(2017)
نبذة مختصرة : International audience ; Visual deficit is one of the complications of Huntington disease (HD), a fatal neurological disorder caused by CAG trinucleotide expansions in the gene, leading to the production of mutant Huntingtin (mHTT) protein. Transgenic HD R6/1 mice expressing human HTT exon1 with 115 CAG repeats recapitulate major features of the human pathology and exhibit a degeneration of the retina. Our aim was to gain insight into the ultrastructure of the pathological HD R6/1 retina by electron microscopy (EM). We show that the HD R6/1 retina is enriched with unusual organelles myelinosomes, produced by retinal neurons and glia. Myelinosomes are present in all nuclear and plexiform layers, in the synaptic terminals of photoreceptors, in the processes of retinal neurons and glial cells, and in the subretinal space. In vitro study shows that myelinosomes secreted by human retinal glial Müller MIO-M1 cells transfected with carry EGFP-mHTT-exon1 protein, as revealed by immuno-EM and Western-blotting. Myelinosomes loaded with mHTT-exon1 are incorporated by naive neuronal/neuroblastoma SH-SY5Y cells. This results in the emergence of mHTT-exon1 in recipient cells. This process is blocked by membrane fusion inhibitor MDL 28170. Conclusion: Incorporation of myelinosomes carrying mHTT-exon1 in recipient cells may contribute to HD spreading in the retina. Exploring ocular fluids for myelinosome presence could bring an additional biomarker for HD diagnostics.
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