Gastric Alpha-Synuclein Immunoreactive Inclusions in Meissner's and Auerbach's Plexuses in Cases Staged for Parkinson's Disease-Related Brain Pathology

Neurosci Lett. 2006 Mar 20;396(1):67-72. doi: 10.1016/j.neulet.2005.11.012. Epub 2005 Dec 5.

Abstract

The progressive degenerative process associated with sporadic Parkinson's disease (sPD) is characterized by formation of alpha-synuclein-containing inclusion bodies in a few types of projection neurons in both the enteric and central nervous systems (ENS and CNS). In the brain, the process apparently begins in the brainstem (dorsal motor nucleus of the vagal nerve) and advances through susceptible regions of the basal mid-and forebrain until it reaches the cerebral cortex. Anatomically, all of the vulnerable brain regions are closely interconnected. Whether the pathological process begins in the brain or elsewhere in the nervous system, however, is still unknown. We therefore used immunocytochemisty to investigate the gastric myenteric and submucosal plexuses in 150 microm cryosections and 8 microm paraffin sections from five autopsy individuals, whose brains were also staged for Parkinson-associated synucleinopathy. alpha-synuclein immunoreactive inclusions were found in neurons of the submucosal Meissner plexus, whose axons project into the gastric mucosa and terminate in direct proximity to fundic glands. These elements could provide the first link in an uninterrupted series of susceptible neurons that extend from the enteric to the central nervous system. The existence of such an unbroken neuronal chain lends support to the hypothesis that a putative environmental pathogen capable of passing the gastric epithelial lining might induce alpha-synuclein misfolding and aggregation in specific cell types of the submucosal plexus and reach the brain via a consecutive series of projection neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Axonal Transport / physiology
  • Brain / metabolism
  • Brain / pathology
  • Brain / physiopathology
  • Disease Transmission, Infectious
  • Female
  • Gastric Mucosa / innervation
  • Gastric Mucosa / physiopathology
  • Humans
  • Inclusion Bodies / metabolism
  • Inclusion Bodies / pathology*
  • Male
  • Middle Aged
  • Models, Neurological
  • Myenteric Plexus / metabolism
  • Myenteric Plexus / pathology
  • Myenteric Plexus / physiopathology*
  • Nerve Net / metabolism
  • Nerve Net / pathology
  • Nerve Net / physiopathology
  • Neural Pathways / metabolism
  • Neural Pathways / pathology
  • Neural Pathways / physiopathology
  • Neurons / metabolism
  • Neurons / pathology*
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Parkinson Disease / physiopathology*
  • Prions / metabolism
  • Protein Folding
  • Submucous Plexus / metabolism
  • Submucous Plexus / pathology
  • Submucous Plexus / physiopathology*
  • Vagus Nerve / metabolism
  • Vagus Nerve / physiopathology
  • alpha-Synuclein / metabolism*

Substances

  • Prions
  • alpha-Synuclein