NR AEPT
AU Glatzel,M.; Heppner,F.L.; Albers,K.M.; Aguzzi,A.
TI Sympathetic innervation of lymphoreticular organs is rate limiting for prion neuroinvasion
QU Neuron 2001 Jul 19; 31(1): 25-34
PT journal article
AB Transmissible spongiform encephalopathies are commonly propagated by extracerebral inoculation of the infectious agent. Indirect evidence suggests that entry into the central nervous system occurs via the peripheral nervous system. Here we have investigated the role of the sympathetic nervous system in prion neuroinvasion. Following intraperitoneal prion inoculation, chemical or immunological sympathectomy delayed or prevented scrapie. Prion titers in spinal cords were drastically reduced at early time points after inoculation. Instead, keratin 14-NGF transgenic mice, whose lymphoid organs are hyperinnervated by sympathetic nerves, showed reduction in scrapie incubation time and, unexpectedly, much higher titers of prion infectivity in spleens. We conclude that sympathetic innervation of lymphoid organs is rate limiting for prion neuroinvasion and that splenic sympathetic nerves may act as extracerebral prion reservoirs.
MH Animal; Animals, Newborn; Antioxidants/pharmacology; Ascorbic Acid/pharmacology; B-Lymphocytes/immunology/pathology; Brain Stem/pathology/*physiopathology; Female; Flow Cytometry; Keratin/genetics/physiology; Lymphatic System/immunology/*innervation/pathology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Growth Factor/genetics/physiology; Oxidopamine; Prions/*pathogenicity; Scrapie/pathology/*physiopathology/prevention & control; Spinal Cord/pathology/*physiopathology; Spleen/immunology/pathology; Support, Non-U.S. Gov't; Sympathectomy, Chemical; Sympathetic Nervous System/*physiology; T-Lymphocytes/immunology/pathology; Time Factors; Vagus Nerve/pathology/physiopathology
AD Institute of Neuropathology, University Hospital Zürich, Schmelzbergstrasse 12, CH-8091, Zürich, Switzerland.
SP englisch
PO USA