title: Premotor parkinsonism models.
abstract: Aside from motor symptoms, Parkinson's disease is associated with a number of non-motor symptoms arising many years before motor signs. The most prevalent and predictive premotor symptoms include olfactory dysfunction, REM sleep behaviour disorder (RBD) and constipation. Several studies in toxin- or gene-based models have specifically investigated these non-motor signs in a premotor context. Altered olfactory discrimination has been reproduced both in toxin- and in gene-based models, and genetic models may also reproduce the underlying pathophysiological mechanisms. Sleep alterations have also been demonstrated, mostly in toxin-based models, and RBD-like features can be demonstrated in non-human primates. Gastrointestinal dysfunction and associated enteric pathology are reproduced both in toxin and genetic models displaying reduced colonic motility and enteric α-synuclein accumulation. This review describes the main premotor symptoms that are recapitulated both in toxin- and in gene-based models, their relevance to the human disease, and their potential to understand the underlying mechanisms of early symptoms and disease progression.
authors.affiliation: Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France. Electronic address: erwan.bezard@u-bordeaux2.fr.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bezard
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Fernagut
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005767:Gastrointestinal Diseases / Q000150:complications; D006801:Humans; D000857:Olfaction Disorders / Q000150:complications; D020734:Parkinsonian Disorders / Q000150:complications* / Q000175:diagnosis*; D062706:Prodromal Symptoms; D012893:Sleep Wake Disorders / Q000150:complications
keywords: Constipation; Non-human primate; Olfactory dysfunction; REM sleep behaviour disorder; Rodent models