Open AccessEarly fine motor impairment and behavioral dysfunction in (Thy‐1)‐h[A30P] alpha‐synuclein mice
Author(s) -
EkmarkLewén Sara,
Lindström Veronica,
Gumucio Astrid,
Ihse Elisabeth,
Behere Anish,
Kahle Philipp J.,
Nordström Eva,
Eriksson Maria,
Erlandsson Anna,
Bergström Joakim,
Ingelsson Martin
Publication year - 2018
Publication title -
brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.915
H-Index - 41
ISSN - 2162-3279
DOI - 10.1002/brb3.915
Subject(s) - alpha synuclein , genetically modified mouse , dopaminergic , tyrosine hydroxylase , rotarod performance test , alpha (finance) , transgene , endocrinology , parkinson's disease , medicine , neuroscience , psychology , biology , disease , dopamine , motor activity , developmental psychology , biochemistry , construct validity , gene , psychometrics
Abstract Introduction Intraneuronal inclusions of alpha‐synuclein are commonly found in the brain of patients with Parkinson's disease and other α‐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.