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Early fine motor impairment and behavioral dysfunction in (Thy-1)-h[A30P] alpha-synuclein mice

Ekmark-Lewén, Sara (författare)
Lindstrom, Veronica (författare)
Gumucio, Astrid (författare)
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Ihse, Elisabet, 1977- (författare)
Behere, Anish (författare)
Kahle, Philipp J. (författare)
Nordstrom, Eva (författare)
Eriksson, Maria (författare)
Erlandsson, Anna (författare)
Bergström, Joakim (författare)
Ingelsson, Martin, 1965- (författare)
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 (utgivare)
WILEY, 2018
2018
Engelska.
Ingår i: Brain and Behavior. - 2162-3279. ; 8:3
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Abstract Ämnesord
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  • Introduction: Intraneuronal inclusions of alpha-synuclein are commonly found in the brain of patients with Parkinson's disease and other a-synucleinopathies. The correlation between alpha-synuclein pathology and symptoms has been studied in various animal models. In (Thy-1)-h[A30P] alpha-synuclein transgenic mice, behavioral and motor abnormalities were reported from 12 and 15 months, respectively. The aim of this study was to investigate whether these mice also display symptoms at earlier time points. Methods: We analyzed gait deficits, locomotion, and behavioral profiles in (Thy-1)-h[A30P] alpha-synuclein and control mice at 2, 8, and 11 months of age. In addition, inflammatory markers, levels of alpha-synuclein oligomers, and tyrosine hydroxylase reactivity were studied. Results: Already at 2 months of age, transgenic mice displayed fine motor impairments in the challenging beam test that progressively increased up to 11 months of age. At 8 months, transgenic mice showed a decreased general activity with increased risk-taking behavior in the multivariate concentric square field test. Neuropathological analyses of 8- and 11-month-old mice revealed accumulation of oligomeric alpha-synuclein in neuronal cell bodies. In addition, a decreased presence of tyrosine hydroxylase suggests a dysregulation of the dopaminergic system in the transgenic mice, which in turn may explain some of the motor impairments observed in this mouse model. Conclusions: Taken together, our results show that the (Thy-1)-h[A30P] alpha-synuclein transgenic mouse model displays early Parkinson's disease-related symptoms with a concomitant downregulation of the dopaminergic system. Thus, this should be an -appropriate model to study early phenotypes of alpha-synucleinopathies.

Ämnesord

Medical and Health Sciences  (hsv)
Basic Medicine  (hsv)
Neurosciences  (hsv)
Medicin och hälsovetenskap  (hsv)
Medicinska och farmaceutiska grundvetenskaper  (hsv)
Neurovetenskaper  (hsv)

Nyckelord

A30P mutation
alpha-synuclein
behavioral outcome
challenging beam test
dementia with Lewy bodies
Helicobacter pylori
multivariate concentric square field test
Parkinson' s disease
transgenic mice
tyrosine hydroxylase

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