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BSE infection of the small short-lived primate Microcebus murinus
Noëlle Bons1, Sylvain Lehmann, Noriyuki Nishida
1Laboratoire de neuromorphologie fonctionnelle, EPHE, université Montpellier-II, 34095 Montpellier, France. bonsn@crit.univ-montp2.fr
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.
Insights
Microcebus murinus (lemurs) are susceptible to bovine spongiform encephalopathy (BSE) via oral or intracerebral routes. This study highlights lemurs as a potential primate model for studying prion disease transmission and neurodegeneration.
Area of Science:
- Neuroscience
- Prion Biology
- Infectious Diseases
Background:
- Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative prion disease.
- Understanding prion disease transmission in primates is crucial for public health.
- Primate models are needed to study the pathogenesis and potential zoonotic risks of BSE.
Purpose of the Study:
- To investigate the susceptibility of Microcebus murinus (lemurs) to BSE and macaque-adapted BSE (MBSE).
- To characterize the incubation period, clinical signs, and pathological changes following BSE/MBSE infection in lemurs.
- To evaluate the lemur as a potential animal model for studying prion diseases in primates.
Main Methods:
- Eleven lemurs were intracerebrally or orally inoculated with BSE or MBSE brain homogenates.
- Immunohistochemistry was used to detect abnormal prion protein (PrP) accumulation.
- Western blot analysis confirmed proteinase K-resistant PrP (PrPres) in infected tissues.
- Neurodegeneration markers, including Tau proteins and amyloid plaques, were assessed.
Main Results:
- Lemurs infected with BSE/MBSE showed behavioral and neurological signs, with abnormal PrP detected in the gut, spleen, and brain.
- PrPres was confirmed in the spleen and brain of MBSE-inoculated animals.
- Neurodegenerative changes, including Tau pathology and amyloid plaques, were observed in all infected lemurs.
- PrPres was found in retinal ganglion cells, indicating widespread PrP deposition.
Conclusions:
- Microcebus murinus is susceptible to BSE infectious agents through both intracerebral and oral routes.
- Lemurs exhibit relatively short incubation periods, making them a valuable model for prion disease research.
- The study demonstrates the utility of lemurs for investigating prion disease pathophysiology and transmission in primates.