Prions spread via the autonomic nervous system from the gut to the central nervous system in cattle incubating bovine spongiform encephalopathy.
To elucidate the still-unknown pathogenesis of bovine spongiform encephalopathy (BSE), an oral BSE challenge and sequential kill study was carried out on 56 calves. Relevant tissues belonging to the peripheral and central nervous system, as well as to the lymphoreticular tract, from necropsied animals were analysed by highly sensitive immunohistochemistry and immunoblotting techniques to reveal the presence of BSE-associated pathological prion protein (PrPSc) depositions. Our results demonstrate two routes involving the autonomic nervous system through which BSE prions spread by anterograde pathways from the gastrointestinal tract (GIT) to the central nervous system (CNS): (i) via the coeliac and mesenteric ganglion complex, splanchnic nerves and the lumbal/caudal thoracic spinal cord (representing the sympathetic GIT innervation); and (ii) via the Nervus vagus (parasympathetic GIT innervation). The dorsal root ganglia seem to be subsequently affected, so it is likely that BSE prion invasion of the non-autonomic peripheral nervous system (e.g. sciatic nerve) is a secondary retrograde event following prion replication in the CNS. Moreover, BSE-associated PrPSc was already detected in the brainstem of an animal 24 months post-infection, which is 8 months earlier than reported previously. These findings are important for the understanding of BSE pathogenesis and for the development of new diagnostic strategies for this infectious disease.
Hoffmann
Christine
C
Institute for Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Boddenblick 5a, 17493 Greifswald-Insel Riems, Germany.
Ziegler
Ute
U
Institute for Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Boddenblick 5a, 17493 Greifswald-Insel Riems, Germany.
Buschmann
Anne
A
Institute for Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Boddenblick 5a, 17493 Greifswald-Insel Riems, Germany.
Weber
Artur
A
Institute for Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Boddenblick 5a, 17493 Greifswald-Insel Riems, Germany.
Kupfer
Leila
L
Institute for Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Boddenblick 5a, 17493 Greifswald-Insel Riems, Germany.
Oelschlegel
Anja
A
Institute for Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Boddenblick 5a, 17493 Greifswald-Insel Riems, Germany.
Hammerschmidt
Baerbel
B
Institute for Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Boddenblick 5a, 17493 Greifswald-Insel Riems, Germany.
Groschup
Martin H
MH
Institute for Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Boddenblick 5a, 17493 Greifswald-Insel Riems, Germany.
D000818:Animals; D001341:Autonomic Nervous System / Q000737:chemistry* / Q000473:pathology; D001933:Brain Stem / Q000737:chemistry / Q000473:pathology; D002417:Cattle; D002490:Central Nervous System / Q000737:chemistry* / Q000473:pathology; D016643:Encephalopathy, Bovine Spongiform / Q000473:pathology*; D005727:Ganglia, Spinal / Q000737:chemistry / Q000473:pathology; D015151:Immunoblotting; D007150:Immunohistochemistry; D008208:Lymphatic System / Q000737:chemistry / Q000473:pathology; D018620:PrPSc Proteins / Q000032:analysis*; D013997:Time Factors
D018620:PrPSc Proteins