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

• Main Authors: Amschl David, Neddens Jörg, Havas Daniel, Flunkert Stefanie, Rabl Roland, Römer Heinrich, Rockenstein Edward, Masliah Eliezer, Windisch Manfred, Hutter-Paier Birgit
• Format: Article
• Language: English
• Published: BMC 2013-01-01
• Series: BMC Neuroscience
• Subjects: Behavior; Immunofluorescence; Motor deficit; Mouse model; Parkinson’s disease; Phosphorylation; Synucleinopathy; α-Synuclein; Transgene
• Online Access: http://www.biomedcentral.com/1471-2202/14/6

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>