Sympathetic Innervation of Lymphoreticular Organs Is Rate Limiting for Prion Neuroinvasion

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...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2001-07, Vol.31 (1), p.25-34
Main Authors: Glatzel, Markus, Heppner, Frank L., Albers, Kathryn M., Aguzzi, Adriano
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Antioxidants - pharmacology
Ascorbic Acid - pharmacology
B-Lymphocytes - immunology
B-Lymphocytes - pathology
Brain Stem - pathology
Brain Stem - physiopathology
Female
Flow Cytometry
Keratins - genetics
Keratins - physiology
Lymphatic System - immunology
Lymphatic System - innervation
Lymphatic System - pathology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Nerve Growth Factor - genetics
Nerve Growth Factor - physiology
Oxidopamine
Prions - pathogenicity
Scrapie - pathology
Scrapie - physiopathology
Scrapie - prevention & control
Spinal Cord - pathology
Spinal Cord - physiopathology
Spleen - immunology
Spleen - pathology
splenic nerve
Sympathectomy, Chemical
Sympathetic Nervous System - physiology
T-Lymphocytes - immunology
T-Lymphocytes - pathology
Time Factors
Vagus Nerve - pathology
Vagus Nerve - physiopathology
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Summary: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.
ISSN:0896-6273
1097-4199
DOI:10.1016/S0896-6273(01)00331-2