title: Early and progressive sensorimotor anomalies in mice overexpressing wild-type human alpha-synuclein.
abstract: Accumulation of alpha-synuclein in brain is a hallmark of synucleinopathies, neurodegenerative diseases that include Parkinson's disease. Mice overexpressing alpha-synuclein under the Thy-1 promoter (ASO) show abnormal accumulation of alpha-synuclein in cortical and subcortical regions of the brain, including the substantia nigra. We examined the motor deficits in ASO mice with a battery of sensorimotor tests that are sensitive to alterations in the nigrostriatal dopaminergic system. Male wild-type and ASO mice were tested every 2 months for 8 months for motor performance and coordination on a challenging beam, inverted grid, and pole, sensorimotor deficits in an adhesive removal test, spontaneous activity in a cylinder, and gait. Fine motor skills were assessed by the ability to grasp cotton from a bin. ASO mice displayed significant impairments in motor performance and coordination and a reduction in spontaneous activity as early as 2 months of age. Motor performance and coordination impairments became progressively worse with age and sensorimotor deficits appeared at 6 months. Fine motor skills were altered at 4 months and worsened at 8 months. These data indicate that overexpression of alpha-synuclein induced an early and progressive behavioral phenotype that can be detected in multiple tests of sensorimotor function. These behavioral deficits provide a useful way to assess novel drug therapy in genetic models of synucleinopathies.
authors.affiliation: Department of Neurology, The Mental Retardation Research Center, The David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California 90095-1769, USA.
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Fleming
authors.forename: Jonathan
authors.initials: J
authors.lastname: Salcedo
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Fernagut
authors.forename: Edward
authors.initials: E
authors.lastname: Rockenstein
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: Michael S
authors.initials: MS
authors.lastname: Levine
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Chesselet
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000503:physiopathology; D005684:Gait / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009048:Motor Skills / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000503:physiopathology*; D011115:Polyneuropathies / Q000378:metabolism / Q000503:physiopathology; D004856:Postural Balance / Q000502:physiology; D011596:Psychomotor Disorders / Q000378:metabolism / Q000503:physiopathology; D011597:Psychomotor Performance / Q000502:physiology; D013378:Substantia Nigra / Q000503:physiopathology; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; C497605:Snca protein, mouse; D051843:Synucleins; D051844:alpha-Synuclein