title: BSE infection of the small short-lived primate Microcebus murinus.
abstract: Eleven Microcebus murinus (lemur) primates were intracerebrally or orally infected by bovine spongiform encephalopathy (BSE) or macaque-adapted BSE (MBSE) brain homogenates. In many BSE and MBSE infected lemurs, but not in animals inoculated with normal bovine brain, persistent behavioral changes occurred as early as 3 months, and neurological signs as early as 13 months after infection. Immunohistochemical examination of animals sacrificed during the incubation period revealed an abnormal accumulation of 'prion' protein (PrP) in the intestinal wall, intestinal nervous plexus, mesenteric lymph nodes and spleen, and in the clinical stage, also in the brain. In MBSE-inoculated animals, proteinase K resistance of the PrP (PrPres) was confirmed by Western blot in the spleen and the brain. Obvious signs of neurodegeneration were observed in all infected animals characterized by hyperaggregated and paired-helical filaments-immunoreactive Tau proteins, beta 42-amyloid plaques and astrogliosis. Additionally, PrPres was present in the ganglion cells of the retina in diseased animals after either intracerebrally or oral infection by the BSE or MBSE agent. These results show that the microcebe is susceptible to the BSE infectious agent via intracerebral and oral routes with comparatively short incubation periods compared to simians, and could be a useful animal model to study the pathophysiology of disease transmission in primates.
authors.affiliation: Laboratoire de neuromorphologie fonctionnelle, EPHE, université Montpellier-II, 34095 Montpellier, France. bonsn@crit.univ-montp2.fr
authors.forename: Noëlle
authors.initials: N
authors.lastname: Bons
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lehmann
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nishida
authors.forename: Nadine
authors.initials: N
authors.lastname: Mestre-Frances
authors.forename: Dominique
authors.initials: D
authors.lastname: Dormont
authors.forename: Patrick
authors.initials: P
authors.lastname: Belli
authors.forename: Andre
authors.initials: A
authors.lastname: Delacourte
authors.forename: Jacques
authors.initials: J
authors.lastname: Grassi
authors.forename: Paul
authors.initials: P
authors.lastname: Brown
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry; D002417:Cattle; D016565:Cheirogaleidae; D004195:Disease Models, Animal; D016643:Encephalopathy, Bovine Spongiform / Q000635:transmission*; D019286:Endopeptidase K / Q000378:metabolism; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D007421:Intestine, Small / Q000737:chemistry; D008198:Lymph Nodes / Q000737:chemistry; D008251:Macaca; D008643:Mesentery; D011328:Prions / Q000032:analysis / Q000378:metabolism; D013154:Spleen / Q000737:chemistry; D014020:Tissue Extracts / Q000008:administration & dosage
chemical_list: D011328:Prions; D014020:Tissue Extracts; D019286:Endopeptidase K