First case of feline spongiform encephalopathy in a captive cheetah born in France: PrPsc analysis in various tissues revealed unexpected targeting of kidney and adrenal gland
Feline spongiform encephalopathy (FSE), affecting domestic and captive feline species, is a prion disease considered to be related to bovine spongiform encephalopathy. Here we report an immunohistological analysis of the first FSE-affected cheetah born in France. The duration of clinical signs, of which ataxia was the main one, was about 8 weeks. The distribution of abnormal prion protein (PrPsc) was studied by immunohistochemistry within 27 different tissues. Different antibodies were used to visualise abnormal PrP deposits in situ. PrPsc accumulation was detected in the central nervous system (cerebral cortex, cerebellum, brain stem, spinal cord, retina), in peripheral nerves and in lymphoid organs. PrPsc deposits were not observed within the enteric nervous system nor in several other organs, such as pancreas, ovary, liver and muscle. More interestingly, unusual PrPsc deposits were observed within the zona fasciculata/reticularis of the adrenal gland and within some glomeruli of the kidney raising the question of possible PrPsc excretion. The sympathetic innervation of these two organs was visualised and compared to the distribution of PrPsc deposits. Our results suggest the possibility that the infectious agent is spread by both haematogenous and nervous pathways.
KeywordsBSE FSE Noradrenergic system Prion vCJD
This work was supported in parts by grants from the "Programme National de Recherches sur les ESST et les Prions". Stéphane Lezmi was financially supported by a grant from Agence Française de Sécurité Sanitaire des Aliments (AFSSA). We gratefully acknowledge Dr. R. Pariaut (Ecole Nationale Vétérinaire de Lyon, France) for helpful discussions.
- Bell JE (1996) Neuropathological diagnosis of human prion disease. PrP immunocytochemical techniques. In: Baker HRRM (ed) Prion disease. Humana, Tottowa, pp 59–83Google Scholar
- Bencsik A, Lezmi S, Baron T (2001) Autonomous nervous system innervation of lymphoid territories in spleen: A possible involvement of noradrenergic neurons for prion neuroinvasion in natural scrapie. J. Neurovirol. 7:447–453.Google Scholar
- Björklund A, Hökfelt T (1985) Handbook of chemical neuroanatomy—Classical transmitters in the CNS. Amsterdam, Elsevier.Google Scholar
- Elsen JM, Amigues Y, Schelcher F, Ducrocq V, Andréoletti O, Eychenne F, Vu Tien Khang J, Poivey JP, Lantier F, Laplanche J-L (1999) Genetic susceptibility and transmission factors in scrapie: detailed analysis of an epidemic in a closed flock of Romanov. Arch Virol 144:431–445CrossRefPubMedGoogle Scholar
- Guyton M, Hall J (2000) Textbook of medical physiology, 10th edn. Saunders, PhiladelphiaGoogle Scholar
- Jeffrey M, McGovern G, Martin S, Goodsir CM, Brown KL (2000) Cellular and sub-cellular localisation of PrP in the lymphoreticular system of mice and sheep. Arch Virol 23–38Google Scholar
- Keulen LJM van, Schreuder BEC, Vromans MEW, Langeveld JPM, Smits MA (2000) Pathogenesis of natural scrapie in sheep. Arch Virol 57–71Google Scholar
- O'Rourke KI, Duncan JV, Logan JR, Anderson AK, Norden DK, Williams ES, Combs BA, Stobart RH, Moss GE, Sutton DL (2002) Active surveillance for scrapie by third eyelid biopsy and genetic susceptibility testing of flocks of sheep in Wyoming. Clin Diagn Lab Immunol 9:966–971CrossRefPubMedGoogle Scholar
- Prusiner SB (1997b) Transmissible encephalopathies (prion diseases). Structural biology and genetics of prions. J Neurovirol 3:S21Google Scholar
- Wolfgang K (1995) Atlas d'histologie, 2nd edn. Médecine-Sciences Flammarion, ParisGoogle Scholar