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

BMC Neuroscience

Research Article

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

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

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

DOI  :  10.1186/1471-2202-14-6

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

来源: Springer

【 摘 要 】

BackgroundProgressive 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.ResultsThese 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.ConclusionThe 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】

Unknown   
© Amschl et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.