title: Microcebus murinus retina: a new model to assess prion-related neurotoxicity in primates.
abstract: No effective treatment currently exists for prion diseases and therefore the development of experimental non-human primate models of prion neurotoxicity, to better understand the underlying mechanism and to test new treatments relevant to humans, represents an urgent medical need. However, the establishment of such models is challenging due to animal welfare and cost considerations. We describe here the use of Microcebus murinus retina, in primary cultures and in vivo, as a new experimental primate model to rapidly examine the effects in the central nervous system of PrP(106-126), a neurotoxic fragment of the human prion protein. We demonstrate that PrP(106-126) triggered rod photoreceptor cell loss by apoptosis and a change in morphology of microglial cells in mixed neuronal-glial cultures of retinal cells. In addition, 2days after intravitreal injection of PrP(106-126), retinas showed a significant increase in the number of apoptotic nuclei, mainly in the ganglion cell layer.
authors.affiliation: Univ Montpellier 2, Montpellier, F-34095 France. joan.torrent@inserm.fr <joan.torrent@inserm.fr>
authors.forename: Joan
authors.initials: J
authors.lastname: Torrent
authors.forename: Chadi
authors.initials: C
authors.lastname: Soukkarieh
authors.forename: Guy
authors.initials: G
authors.lastname: Lenaers
authors.forename: Carl
authors.initials: C
authors.lastname: Arndt
authors.forename: Valérie
authors.initials: V
authors.lastname: Forster
authors.forename: Serge
authors.initials: S
authors.lastname: Picaud
authors.forename: Nadine
authors.initials: N
authors.lastname: Mestre-Francés
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Verdier
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D016565:Cheirogaleidae; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020287:In Situ Nick-End Labeling / Q000379:methods; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000473:pathology*; D010320:Parvalbumins / Q000378:metabolism; D010446:Peptide Fragments / Q000633:toxicity; D011328:Prions / Q000378:metabolism* / Q000633:toxicity; D012160:Retina / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D012243:Rhodopsin / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D010320:Parvalbumins; D010446:Peptide Fragments; D011328:Prions; D014746:Vimentin; C082632:prion protein (106-126); D012243:Rhodopsin