title: The novel adaptive rotating beam test unmasks sensorimotor impairments in a transgenic mouse model of Parkinson's disease.
abstract: Development of disease modifying therapeutics for Parkinson's disease (PD), the second most common neurodegenerative disorder, relies on availability of animal models which recapitulate the disease hallmarks. Only few transgenic mouse models, which mimic overexpression of alpha-synuclein, show dopamine loss, behavioral impairments and protein aggregation. Mice overexpressing human wildtype alpha-synuclein under the Thy-1 promotor (Thy1-aSyn) replicate these features. However, female mice do not exhibit a phenotype. This was attributed to a potentially lower transgene expression located on the X chromosome. Here we support that female mice overexpress human wildtype alpha-synuclein only about 1.5 fold in the substantia nigra, compared to about 3 fold in male mice. Since female Thy1-aSyn mice were shown previously to exhibit differences in corticostriatal communication and synaptic plasticity similar to their male counterparts we hypothesized that female mice use compensatory mechanisms and strategies to not show overt motor deficits despite an underlying endophenotype. In order to unmask these deficits we translated recent findings in PD patients that sensory abnormalities can enhance motor dysfunction into a novel behavioral test, the adaptive rotating beam test. We found that under changing sensory input female Thy1-aSyn mice showed an overt phenotype. Our data supports that the integration of sensorimotor information is likely a major contributor to symptoms of movement disorders and that even low levels of overexpression of human wildtype alpha-synuclein has the potential to disrupt processing of these information. The here described adaptive rotating beam test represents a sensitive behavioral test to detect moderate sensorimotor alterations in mouse models.
authors.affiliation: Institute of Pharmacology, Pharmacy and Toxicology, Department of Veterinary Medicine, Leipzig University, An den Tierkliniken 15, 04103 Leipzig, Germany. Electronic address: julia.gerstenberger@vetmed.uni-leipzig.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Gerstenberger
authors.affiliation: Institute of Pharmacology, Pharmacy and Toxicology, Department of Veterinary Medicine, Leipzig University, An den Tierkliniken 15, 04103 Leipzig, Germany. Electronic address: anne.bauer@vetmed.uni-leipzig.de.
authors.forename: Anne
authors.initials: A
authors.lastname: Bauer
authors.affiliation: Institute of Pharmacology, Pharmacy and Toxicology, Department of Veterinary Medicine, Leipzig University, An den Tierkliniken 15, 04103 Leipzig, Germany. Electronic address: christin.helmschrodt@uni-leipzig.de.
authors.forename: Christin
authors.initials: C
authors.lastname: Helmschrodt
authors.affiliation: Institute of Pharmacology, Pharmacy and Toxicology, Department of Veterinary Medicine, Leipzig University, An den Tierkliniken 15, 04103 Leipzig, Germany. Electronic address: angelika.richter@vetmed.uni-leipzig.de.
authors.forename: Angelika
authors.initials: A
authors.lastname: Richter
authors.affiliation: Institute of Pharmacology, Pharmacy and Toxicology, Department of Veterinary Medicine, Leipzig University, An den Tierkliniken 15, 04103 Leipzig, Germany. Electronic address: franziska.richter@vmf.uni-leipzig.de.
authors.forename: Franziska
authors.initials: F
authors.lastname: Richter
mesh_terms: D000223:Adaptation, Psychological / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D020233:Gait Disorders, Neurologic / Q000175:diagnosis* / Q000209:etiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009759:Nystagmus, Pathologic / Q000209:etiology*; D010300:Parkinson Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012737:Sex Factors; D013378:Substantia Nigra / Q000378:metabolism; D013997:Time Factors; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D051844:alpha-Synuclein
keywords: Alpha-synuclein; Parkinson’s disease; Phenotype; Sensorimotor impairments; Transgenic mice