That's interesting, Rick!

Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen
Journal Journal of Neural Transmission
Publisher Springer Wien
ISSN 0300-9564 (Print) 1435-1463 (Online)
Subject Biomedical and Life Sciences and Medicine
Issue Volume 110, Number 5 / May, 2003
DOI 10.1007/s00702-002-0808-2
Pages 517-536
Online Date Thursday, February 19, 2004

Authors
H. Braak, U. Rüb, W. P. Gai, K. Del Tredici
Abstract

Summary. The progressive, neurodegenerative process underlying idiopathic Parkinson's disease is associated with the formation of proteinaceous inclusion bodies that involve a few susceptible neuronal types of the human nervous system. In the lower brain stem, the process begins in the dorsal motor nucleus of the vagus nerve and advances from there essentially upwards through susceptible regions of the medulla oblongata, pontine tegmentum, midbrain, and basal forebrain until it reaches the cerebral cortex.


With time, multiple components of the autonomic, limbic, and motor systems become severely impaired. All of the vulnerable subcortical grays and cortical areas are closely interconnected. Incidental cases of idiopathic Parkinson's disease may show involvement of both the enteric nervous system and the dorsal motor nucleus of the vagus nerve.


This observation, combined with the working hypothesis that the stereotypic topographic expansion pattern of the lesions may resemble that of a falling row of dominos, prompts the question whether the disorder might originate outside of the central nervous system, caused by a yet unidentified pathogen that is capable of passing the mucosal barrier of the gastrointestinal tract and, via postganglionic enteric neurons, entering the central nervous system along unmyelinated praeganglionic fibers generated from the visceromotor projection cells of the vagus nerve.

By way of retrograde axonal and transneuronal transport, such a causative pathogen could reach selectively vulnerable subcortical nuclei and, unimpeded, gain access to the cerebral cortex. The here hypothesized mechanism offers one possible explanation for the sequential and apparently uninterrupted manner in which vulnerable brain regions, subcortical grays and cortical areas become involved in idiopathic Parkinson's disease.


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Role of inflammation in gastrointestinal tract in aetiology and pathogenesis of idiopathic parkinsonism

http://www.blackwell-synergy.com/doi...im.2005.01.011

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: Neurosci Lett. 2006 Jun 19;401(1-2):146-9. Epub 2006 Apr 4.

Intragastric proteasome inhibition induces alpha-synuclein-immunopositive aggregations in neurons in the dorsal motor nucleus of the vagus in rats.

Miwa H, Kubo T, Suzuki A, Kondo T.

Department of Neurology, Wakayama Medical University, 811-1 Kimiidera, Wakayama-city, Wakayama 641-8510, Japan. h-miwa@wakayama-med.ac.jp

The neuropathological hallmark of idiopathic Parkinson's disease (PD) is dopaminergic neuron degeneration in the substantia nigra. However, it has been suggested that the neurodegenerative process initially may occur in the dorsal motor nucleus of the vagus (DMV). This implies that unidentified environmental toxins or neurotropic pathogens that is capable of passing the mucosal barrier of the gastrointestinal tract might affect the enteric nerve endings of the vagal neurons, possibly resulting in retrograde degeneration of the DMV.

The present study aimed to evaluate the effects of proteasome inhibition of the intragastric nerve terminals of the DMV in rats. Following multiple injections of PSI, a selective proteasome inhibitor, or vehicle into the ventral wall of the stomach, the medulla oblongata was studied immunohistologically. In the DMV neurons of rats treated with PSI but not vehicle, alpha-synuclein-immunopositive intracytoplasmic inclusions and activated microglia were observed, predominantly in the left DMV. However, there was no significant loss of neurons.

These results suggest that intragastric proteasome inhibition has a retrograde effect on DMV neurons but is insufficient to induce cell death, suggesting no causal linkage between inclusion body formation with proteasome inhibition and neuron death in the DMV. This might also implicate that Lewy body formation in the DMV in PD is possibly related to peroral invasion of environmental toxins that inhibit ubiquitin-proteasome system function.

full article:

http://www.sciencedirect.com/science...d0e93e428aca90