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. 2004 Oct 20;24(42):9434-40.
doi: 10.1523/JNEUROSCI.3080-04.2004.

Early and progressive sensorimotor anomalies in mice overexpressing wild-type human alpha-synuclein

Sheila M Fleming  1 , Jonathan Salcedo, Pierre-Olivier Fernagut, Edward Rockenstein, Eliezer Masliah, Michael S Levine, Marie-Françoise Chesselet
Affiliations

Early and progressive sensorimotor anomalies in mice overexpressing wild-type human alpha-synuclein

Sheila M Fleming et al. J Neurosci. .

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.

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Figures

Figure 1.
Figure 1.
ASO mice were weighed before behavioral testing at 2, 4, 6, and 8 months of age. ASO (n = 7) mice weighed significantly lessthan wild-type (n = 17) mice at all ages. Values are expressed as mean weight (in grams) ± SEM; **p < 0.01 compared with wild type.
Figure 2.
Figure 2.
Motor performance and coordination was measured in ASO (n = 7) and wild-type (n = 17) mice using the challenging beam. Errors per step (A), number of steps (B), and time to traverse (C) were measured at 2, 4, 6, and 8 months of age. ASO mice made more errors and steps and took longer to traverse the beam compared with wild-type mice. In addition, ASO impairments worsened over time. Values are expressed as mean ± SEM. *p < 0.05 and **p < 0.01, compared with wild-type mice at the same age; ΔΔp < 0.01, compared with previous ages tested within the ASO group.
Figure 3.
Figure 3.
Adhesive removal was measured in ASO (n = 7) and wild-type (n = 17) mice at 2, 4, 6, and 8 months of age. At 6 months of age, ASO mice were significantly slower to respond to sensory stimuli compared with wild-type mice (A). The time from stimulus contact to stimulus removal did not differ between ASO and wild-type mice (B). Values are expressed as means ± SEM. *p < 0.05, compared with wild-type mice.
Figure 4.
Figure 4.
Spontaneous activity in ASO (n = 7) and wild-type (n = 17) mice at 2, 4, 6, and 8 months of age. Rearing (A), forelimb (B) and hindlimb (C) steps, and time spent grooming (D) were measured. ASO mice were less active in all measures compared with wild-type mice. Values are expressed as mean ± SEM. *p < 0.05 and **p < 0.01, compared with wild-type mice.
Figure 5.
Figure 5.
Bin cotton use in ASO and wild-type mice at 4 (A; n = 8) and 8 (B, C; n = 12) months of age. Separate groups of ASO mice shredded significantly less cotton compared with wild-type mice. Cotton was placed inside the cage of 8-month-old ASO mice to demonstrate that ASO mice can make nests (C). Values are expressed as mean ± SEM. *p < 0.05 and **p < 0.01, compared with wild-type mice.
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References

    1. Barlow C, Hirotsune S, Paylor R, Liyanage M, Eckhaus M, Collins F, Shiloh Y, Crawley JN, Ried T, Tagle D, Wynshaw-Boris A (1996) Atm-deficient mice: a paradigm of ataxia telangiectasia. Cell 86: 159-171. - PubMed
    1. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 24: 197-211. - PubMed
    1. Broida J, Svare B (1982) Strain-typical patterns of pregnancy-induced nest-building in mice: maternal and experiential influences. Physiol Behav 29: 53-57. - PubMed
    1. Brooks DJ, Frey KA, Marek KL, Oakes D, Paty D, Prentice R, Shults CW, Stoessl AJ (2003) Assessment of neuroimaging techniques as biomarkers of the progression of Parkinson's disease. Exp Neurol 184[Suppl 1]: 68-79. - PubMed
    1. Carter RJ, Lione LA, Humby T, Mangiarini L, Mahal A, Bates GP, Dunnett SB, Morton AJ (1999) Characterization of progressive motor deficits in mice transgenic for the human Huntington's disease mutation. J Neurosci 19: 3248-3257. - PMC - PubMed

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