title: Anatomical evidence for ileal Peyer's patches innervation by enteric nervous system: a potential route for prion neuroinvasion?
abstract: We have examined the innervation of the gut-associated lymphoid system of the sheep ileum, with a view to identifying potential sites for neuroinvasion by pathogens, such as prions (PrP(Sc)). Special attention has been paid to the follicles of Peyer's patches (PPs), which are major sites of PrP(Sc) accumulation during infection. Evidence exists that the enteric nervous system, together with the parasympathetic and sympathetic pathways projecting to the intestine, are important for PrP(Sc) entry into the central nervous system. Thus, PrP(Sc) might move from PPs to the neurons and nerve fibres that innervate them. We investigated, by immunohistochemistry and retrograde tracing (DiI) from the follicles, the distribution and phenotype of enteric neurons innervating the follicles. Antibodies against protein gene product 9.5, tyrosine hydroxylase, dopamine beta hydroxylase, choline acetyltransferase, calbindin (CALB), calcitonin gene-related peptide (CGRP), and nitric oxide synthase were used to characterise the neurons. Immunoreactivity for each of these was observed in fibres around and inside PP follicles. CGRP-immunoreactive fibres were mainly seen at the follicular dome. Retrograde tracing revealed submucosal neurons that contributed to the innervation of PPs, including Dogiel type II neurons and neurons immunoreactive for CALB and CGRP. The major source of the adrenergic fibres are the sympathetic ganglia. Our results thus suggest that enteric and sympathetic neurons are involved during the first stage of neuroinvasion, with neurons connecting to them acting as potential carriers of PrP(Sc) to the central nervous system.
authors.affiliation: Department of Veterinary Morphophysiology and Animal Productions, University of Bologna, 40064 Ozzano Emilia, Bologna, Italy. roberto.chiocchetti@unibo.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Chiocchetti
authors.forename: Gemma
authors.initials: G
authors.lastname: Mazzuoli
authors.forename: Valeria
authors.initials: V
authors.lastname: Albanese
authors.forename: Maurizio
authors.initials: M
authors.lastname: Mazzoni
authors.forename: Paolo
authors.initials: P
authors.lastname: Clavenzani
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lalatta-Costerbosa
authors.forename: Maria L
authors.initials: ML
authors.lastname: Lucchi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Guardo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Marruchella
authors.forename: John B
authors.initials: JB
authors.lastname: Furness
mesh_terms: D000818:Animals; D064026:Calbindins; D002232:Carbocyanines / Q000378:metabolism; D002417:Cattle; D002795:Choline O-Acetyltransferase / Q000032:analysis; D004299:Dopamine beta-Hydroxylase / Q000032:analysis; D017615:Enteric Nervous System / Q000166:cytology* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D007082:Ileum / Q000166:cytology / Q000294:innervation* / Q000378:metabolism; D009412:Nerve Fibers / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000032:analysis; D009924:Organ Culture Techniques; D010581:Peyer's Patches / Q000166:cytology / Q000294:innervation* / Q000378:metabolism; D011328:Prions / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000032:analysis; D012756:Sheep; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis; D043222:Ubiquitin Thiolesterase / Q000032:analysis
chemical_list: D064026:Calbindins; D002232:Carbocyanines; D005456:Fluorescent Dyes; D011328:Prions; D064030:S100 Calcium Binding Protein G; C024286:3,3'-dioctadecylindocarbocyanine; D019001:Nitric Oxide Synthase; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D002795:Choline O-Acetyltransferase; D043222:Ubiquitin Thiolesterase