title: Effects of oral administration of rotenone on gastrointestinal functions in mice.
abstract: BACKGROUND
  The systemic rotenone model of Parkinson's disease (PD) accurately replicates many aspects of the pathology of human PD, especially neurodegeneration of the substantia nigra and lesions in the enteric nervous system (ENS). Nevertheless, the precise effects of oral rotenone on the ENS have not been addressed yet. This study was therefore designed to assess the effects of a chronic oral treatment by rotenone on enteric neurochemical phenotype, gastrointestinal (GI) motility, and intestinal epithelial barrier permeability.
  
  
  METHODS
  Male C57BL6N mice received once daily oral rotenone administration for 28 days. GI functions were analyzed 4 weeks after rotenone treatment. Gastrointestinal motility was assessed by measuring gastric emptying, total transit time, fecal pellet output, and bead latency. Intestinal barrier permeability was evaluated both in vivo and ex vivo. The number of enteric neurons and the enteric neurochemical phenotype were analyzed by immunohistochemistry. Tyrosine hydroxylase (TH) immunostaining of dopaminergic neurons of the substantia nigra was performed in a subset of animals.
  
  
  RESULTS
  Mice treated orally with rotenone had a decrease in fecal pellet output and in jejunal alpha-synuclein expression as compared with control animals. This was associated with a significant decrease in TH-immunoreactive neurons in the substantia nigra. No change in gastric emptying, total transit time, intestinal epithelial barrier permeability, and enteric neurochemical phenotype was observed.
  
  
  CONCLUSIONS
  Chronic oral treatment with rotenone only induced minor changes in the ENS and did not recapitulate the GI abnormalities seen in PD, while it replicates neurodegeneration of the substantia nigra.
authors.affiliation: Inserm, U913, Nantes, France.
authors.forename: M
authors.initials: M
authors.lastname: Tasselli
authors.forename: T
authors.initials: T
authors.lastname: Chaumette
authors.forename: S
authors.initials: S
authors.lastname: Paillusson
authors.forename: Y
authors.initials: Y
authors.lastname: Monnet
authors.forename: A
authors.initials: A
authors.lastname: Lafoux
authors.forename: C
authors.initials: C
authors.lastname: Huchet-Cadiou
authors.forename: P
authors.initials: P
authors.lastname: Aubert
authors.forename: S
authors.initials: S
authors.lastname: Hunot
authors.forename: P
authors.initials: P
authors.lastname: Derkinderen
authors.forename: M
authors.initials: M
authors.lastname: Neunlist
mesh_terms: D000284:Administration, Oral; D000818:Animals; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009197:Myenteric Plexus / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D012402:Rotenone / Q000008:administration & dosage / Q000633:toxicity*; D013378:Substantia Nigra / Q000187:drug effects; D014475:Uncoupling Agents / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D014475:Uncoupling Agents; D012402:Rotenone