Time course and progression of wild type α-synuclein accumulation in a transgenic mouse model.
BMC Neurosci
; 14: 6, 2013 Jan 09.
Article
em En
| MEDLINE
| ID: mdl-23302418
ABSTRACT
BACKGROUND:
Progressive accumulation of α-synuclein (α-Syn) protein in different brain regions is a hallmark of synucleinopathic diseases, such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. α-Syn transgenic mouse models have been developed to investigate the effects of α-Syn accumulation on behavioral deficits and neuropathology. However, the onset and progression of pathology in α-Syn transgenic mice have not been fully characterized. For this purpose we investigated the time course of behavioral deficits and neuropathology in PDGF-ß human wild type α-Syn transgenic mice (D-Line) between 3 and 12 months of age.RESULTS:
These mice showed progressive impairment of motor coordination of the limbs that resulted in significant differences compared to non-transgenic littermates at 9 and 12 months of age. Biochemical and immunohistological analyses revealed constantly increasing levels of human α-Syn in different brain areas. Human α-Syn was expressed particularly in somata and neurites of a subset of neocortical and limbic system neurons. Most of these neurons showed immunoreactivity for phosphorylated human α-Syn confined to nuclei and perinuclear cytoplasm. Analyses of the phenotype of α-Syn expressing cells revealed strong expression in dopaminergic olfactory bulb neurons, subsets of GABAergic interneurons and glutamatergic principal cells throughout the telencephalon. We also found human α-Syn expression in immature neurons of both the ventricular zone and the rostral migratory stream, but not in the dentate gyrus.CONCLUSION:
The present study demonstrates that the PDGF-ß α-Syn transgenic mouse model presents with early and progressive accumulation of human α-Syn that is accompanied by motor deficits. This information is essential for the design of therapeutical studies of synucleinopathies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
/
Proteínas de Filamentos Intermediários
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Transtornos dos Movimentos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
BMC Neurosci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Áustria