Abstract
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.
Similar content being viewed by others
References
Baron T, Belli P, Madec JY, Moutou F, Vitaud C, Savey M (1997) Spongiform encephalopathy in an imported cheetah in France. Vet Rec 141:270–271
Beekes M, Baldauf E, Diringer H (1996) Sequential appearance and accumulation of pathognomonic markers in the central nervous system of hamsters orally infected with scrapie. J Gen Virol 77:1925–1934
Bell JE (1996) Neuropathological diagnosis of human prion disease. PrP immunocytochemical techniques. In: Baker HRRM (ed) Prion disease. Humana, Tottowa, pp 59–83
Bell JE, Gentleman SM, Ironside JW, McCardle L, Lantos PL, Doey L, Lowe J, Fergusson J, Luthert P, McQuaid S, Allen IV (1997) Prion protein immunocytochemistry: UK five centre consensus report. Neuropathol Appl Neurobiol 23:26–35
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.
Björklund A, Hökfelt T (1985) Handbook of chemical neuroanatomy—Classical transmitters in the CNS. Amsterdam, Elsevier.
Bolton DC, McKinley MP, Prusiner SB (1982) Identification of a protein that purifies with the scrapie prion. Science 218:1309–1311
Bratberg B, Ueland K, Wells G (1995) Feline spongiform encephalopathy in a cat in Norway. Vet Rec 136:444
Collinge J, Sidle KCL, Meads J, Ironside J, Hill AF (1996) Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD. Nature 383:685–690
Debeer SOS, Baron TGM, Bencsik AA (2001) Immunohistochemistry of PrPsc within bovine spongiform encephalopathy brain samples with graded autolysis. J Histochem Cytochem 49:1519–1524
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 144:431–445
Ettaiche M, Pichot R, Vincent JP, Chabry J (2000) In vivo cytotoxicity of the prion protein fragment 106–126. J Biol Chem 275:36487–36490
Fraser H, Pearson GR, McConnell I, Bruce ME, Wyatt JM, Gruffydd-Jones TJ (1994) Transmission of feline spongiform encephalopathy to mice. Vet Rec 134:449–449
Gayrard V, Picard-Hagen N, Grino M, Sauze N, Grandjean C, Galea J, Andreoletti O, Schelcher F, Toutain PL (2000) Major hypercorticism is an endocrine feature of ewes with naturally occurring scrapie. Endocrinology 141:988–994
Glatzel M, Aguzzi A (2000) PrPC expression in the peripheral nervous system is a determinant of prion neuroinvasion. J Gen Virol 81:2813–2821
Groschup M, Weiland F, Straub O, Pfaff E (1996) Detection of scrapie agent in the peripheral nervous system of a diseased sheep. Neurobiol Dis 3:191–195
Guyton M, Hall J (2000) Textbook of medical physiology, 10th edn. Saunders, Philadelphia
Head MW, Northcott V, Rennison K, Ritchie D, McCardle L, Bunn TJR, McLennan NF, Ironside JW, Tullo AB, Bonshek RE (2003) Prion protein accumulation in eyes of patients with sporadic and variant Creutzfeldt-Jakob disease. Invest Ophthalmol Vis Sci 44:342–346
Hill A, Desbruslais M, Joiner S, Sidle KCL, Gowland I, Collinge J (1997) The same prion strain causes vCJD and BSE. Nature 389:448–450
Hill AF, Butterworth RJ, Joiner S, Jackson G, Rossor MN, Thomas DJ, Frosh A (1999) Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 353:183–189
Hunter N, Foster JD, Goldmann W, Stear MJ, Hope J, Bostock C (1996) Natural scrapie in a closed flock of Cheviot sheep occurs only in specific PrP genotypes. Arch Virol 141:809–824
Hunter N, Foster J, Chong A, McCutcheon S, Parnham D, Eaton S, MacKenzie C, Houston F (2002) Transmission of prion diseases by blood transfusion. J Gen Virol 83:2897–2905
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 23–38
Jeffrey M, Martin S, Thomson JR, Dingwall WS, BegaraMcGorum I, Gonzalez L (2001) Onset and distribution of tissue PrP accumulation in scrapie-affected Suffolk sheep as demonstrated by sequential necropsies and tonsillar biopsies. J Comp Pathol 125:48–57
Katz BJ, Warner JE, Digre KB, Creel DJ (2000) Selective loss of the electroretinogram B-wave in a patient with Creutzfeldt-Jakob disease. J Neuroophthalmol 20:116–118
Keulen LJM van, Schreuder BEC, Meloen RH, Mooij-Harkes G, Vromans MEW, Langeveld JPM (1996) Immunohistochemical detection of prion in lymphoid tissues of sheep with natural scrapie. J Clin Microbiol 34:1228–1231
Keulen LJM van, Schreuder BEC, Vromans MEW, Langeveld JPM, Smits MA (1999) Scrapie-associated prion protein in the gastro-intestinal tract of sheep with natural scrapie. J Comp Pathol 121:55–63
Keulen LJM van, Schreuder BEC, Vromans MEW, Langeveld JPM, Smits MA (2000) Pathogenesis of natural scrapie in sheep. Arch Virol 57–71
Kim Y, Carp R, Callahan S, Wisniewski H (1988) Adrenal involvement in scrapie-induced obesity. Proc Soc Exp Biol Med 189:21–27
Kovacs GG, Head MW, Hegyi I, Bunn TJ, Flicker H, Hainfellner JA, McCardle L, Laszlo L, Jarius C, Ironside JW, Budka H (2002) Immunohistochemistry for the prion protein: comparison of different monoclonal antibodies in human prion disease subtypes. Brain Pathol 12:1–11
Lezmi S, Bencsik A, Baron T (2001) CNA42 monoclonal antibody identifies FDC as PrPsc accumulating cells in the spleen of scrapie affected sheep. Vet Immunol Immunopathol 82:1–8
McBride PA, SchulzSchaeffer WJ, Donaldson M, Bruce M, Diringer H, Kretzschmar HA, Beekes M (2001) Early spread of scrapie from the gastrointestinal tract to the central nervous system involves autonomic fibers of the splanchnic and vagus nerves. J Virol 75:9320–9327
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 9:966–971
Peet R, Curran J (1992) Spongiform encephalopathy in an imported cheetah (Acinonyx jubatus). Aust Vet J 69:171
Prusiner SB (1982) Novel proteinaceous infectious particles cause scrapie. Science 216:136–144
Prusiner SB (1997a) Prion diseases and the BSE crisis. Science 278:245–251
Prusiner SB (1997b) Transmissible encephalopathies (prion diseases). Structural biology and genetics of prions. J Neurovirol 3:S21
Ryder SJ, Wells GAH, Bradshaw JM, Pearson GR (2001) Inconsistent detection of PrP in extraneural tissues of cats with feline spongiform encephalopathy. Vet Rec 148:437–441
Schelcher F, Picard-Hagen N, Laroute V, Gayrard V, Popot MA, Andreoletti O, Toutain PL (1999) Corticoid concentrations are increased in the plasma and urine of ewes with naturally occurring scrapie. Endocrinology 140:2422–2425
Shaked GM, Shaked Y, KarivInbal Z, Halimi M, Avraham I, Gabizon R (2001) A protease-resistant prion protein isoform is present in urine of animals and humans affected with prion diseases. J Biol Cell 276:31479–31482
Sigurdson CJ, Spraker TR, Miller MW, Oesch B, Hoover EA (2001) PrPCWD in the myenteric plexus, vagosympathetic trunk and endocrine glands of deer with chronic wasting disease. J Gen Virol 82:2327–2334
Somerville RA, Birkett CR, Farquhar CF, Hunter N, Goldmann W, Dornan J, Grover D, Hennion RM, Percy C, Foster J, Jeffrey M (1997) Immunodetection of PrPsc in spleens of some scrapie-infected sheep but not BSE-infected cows. J Gen Virol 78:2389–2396
Wadsworth JDF, Joiner S, Hill AF, Campbell TA, Desbruslais M, Luthert PJ, Collinge J (2001) Tissue distribution of protease resistant prion protein in variant Creutzfeldt-Jakob disease using a highly sensitive immunoblotting assay. Lancet 358:171–180
Wells GAH, Scott AC, Johnson CT, Gunning RF, Hancock RD, Jeffrey M, Dawson M, Bradley R (1987) A novel progressive spongiform encephalopathy in cattle. Vet Rec 121:419–420
Willoughby D, Kelly D, Lyon D, Wells G (1992) Spongiform encephalopathy in a captive puma. Vet Rec 131:431–434
Wolfgang K (1995) Atlas d'histologie, 2nd edn. Médecine-Sciences Flammarion, Paris
Wyatt JM, Pearson GR, Smerdon TN, Gruffydd-Jones TJ, Wells GAH, Wilesmith JW (1991) Naturally occurring scrapie-like encephalopathy in five domestic cats. Vet Rec 129:233–236
Acknowledgements
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lezmi, S., Bencsik, A., Monks, E. et al. 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. Histochem Cell Biol 119, 415–422 (2003). https://doi.org/10.1007/s00418-003-0524-5
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00418-003-0524-5