BSE infection of the small short-lived primate Microcebus murinus.
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.
Bons
Noëlle
N
Laboratoire de neuromorphologie fonctionnelle, EPHE, université Montpellier-II, 34095 Montpellier, France. bonsn@crit.univ-montp2.fr
Lehmann
Sylvain
S
Nishida
Noriyuki
N
Mestre-Frances
Nadine
N
Dormont
Dominique
D
Belli
Patrick
P
Delacourte
Andre
A
Grassi
Jacques
J
Brown
Paul
P
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
D011328:Prions; D014020:Tissue Extracts; D019286:Endopeptidase K