Neuroinvasion in sheep transmissible spongiform encephalopathies: the role of the haematogenous route

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Abstract

S. Sisó, M. Jeffrey and L. González (2009) Neuropathology and Applied Neurobiology35, 232–246

Neuroinvasion in sheep transmissible spongiform encephalopathies: the role of the haematogenous route

Background:

It is generally believed that after oral exposure to transmissible spongiform encephalopathy (TSE) agents, neuroinvasion occurs via the enteric nervous system (ENS) and the autonomic nervous system. As a result, the dorsal motor nucleus of the vagus nerve is the initial point of disease-associated prion protein (PrPd) accumulation in the brain.

Hypothesis and aim:

If direct ENS invasion following oral infection results in an early and specific brain targeting for PrPd accumulation, such topographical distribution could be different when other routes of infection were used, highlighting distinct routes for neuroinvasion.

Methods:

An immunohistochemical study has been conducted on the brain of 67 preclinically infected sheep exposed to natural scrapie or to experimental TSE infection by various routes.

Results:

Initial PrPd accumulation consistently occurred in the dorsal motor nucleus of the vagus nerve followed by the hypothalamus, regardless of the breed of sheep, PrP genotype, TSE source and, notably, route of infection; these factors did not appear to affect the topographical progression of PrPd deposition in the brain either. Moreover, the early and consistent appearance of PrPd aggregates in the circumventricular organs, where the blood–brain barrier is absent, suggests that these organs can provide a portal for entry of prions when infectivity is present in blood.

Conclusions:

The haematogenous route, therefore, can represent a parallel or alternative pathway of neuroinvasion to ascending infection via the ENS/autonomic nervous system.

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