Time course and progression of wild type α-Synuclein accumulation in a transgenic mouse model

BMC Neuroscience

Birgit Hutter-Paier³  Manfred Windisch³  Eliezer Masliah¹  Edward Rockenstein¹  Heinrich Römer²  Roland Rabl³  Stefanie Flunkert³  Daniel Havas³  Jörg Neddens³  David Amschl³ 

[1] Department of Pathology, University of California San Diego, La Jolla, CA, USA;Karl Franzens University, Institute of Zoology, Graz, 8010, Austria;QPS Austria GmbH, Parkring 12, Grambach, 8074, Austria

关键词: Transgene;    α-Synuclein;    Synucleinopathy;    Phosphorylation;    Parkinson’s disease;    Mouse model;    Motor deficit;    Immunofluorescence;    Behavior;   

Others  :  1140537
DOI  :  10.1186/1471-2202-14-6

 received in 2012-07-10, accepted in 2013-01-03,  发布年份 2013

【 摘 要 】

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-β 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-β 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.

【 授权许可】

   
2013 Amschl et al.; licensee BioMed Central Ltd.

【 图 表 】

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