%0 Journal Article %T Time course and progression of wild type ¦Á-Synuclein accumulation in a transgenic mouse model %A Amschl David %A Neddens J£¿rg %A Havas Daniel %A Flunkert Stefanie %J BMC Neuroscience %D 2013 %I BioMed Central %R 10.1186/1471-2202-14-6 %X Background Progressive accumulation of ¦Á-synuclein (¦Á-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. ¦Á-Syn transgenic mouse models have been developed to investigate the effects of ¦Á-Syn accumulation on behavioral deficits and neuropathology. However, the onset and progression of pathology in ¦Á-Syn transgenic mice have not been fully characterized. For this purpose we investigated the time course of behavioral deficits and neuropathology in PDGF-¦Â human wild type ¦Á-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 ¦Á-Syn in different brain areas. Human ¦Á-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 ¦Á-Syn confined to nuclei and perinuclear cytoplasm. Analyses of the phenotype of ¦Á-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 ¦Á-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-¦Â ¦Á-Syn transgenic mouse model presents with early and progressive accumulation of human ¦Á-Syn that is accompanied by motor deficits. This information is essential for the design of therapeutical studies of synucleinopathies. %K Behavior %K Immunofluorescence %K Motor deficit %K Mouse model %K Parkinson¡¯s disease %K Phosphorylation %K Synucleinopathy %K ¦Á-Synuclein %K Transgene %U http://www.biomedcentral.com/1471-2202/14/6