title: Time course and progression of wild type α-synuclein accumulation in a transgenic mouse model.
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-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: QPS Austria GmbH, Parkring 12, Grambach 8074, Austria.
authors.forename: David
authors.initials: D
authors.lastname: Amschl
authors.forename: Jörg
authors.initials: J
authors.lastname: Neddens
authors.forename: Daniel
authors.initials: D
authors.lastname: Havas
authors.forename: Stefanie
authors.initials: S
authors.lastname: Flunkert
authors.forename: Roland
authors.initials: R
authors.lastname: Rabl
authors.forename: Heinrich
authors.initials: H
authors.lastname: Römer
authors.forename: Edward
authors.initials: E
authors.lastname: Rockenstein
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: Manfred
authors.initials: M
authors.lastname: Windisch
authors.forename: Birgit
authors.initials: B
authors.lastname: Hutter-Paier
mesh_terms: D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009069:Movement Disorders / Q000235:genetics* / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D013997:Time Factors
chemical_list: D007381:Intermediate Filament Proteins; D010982:Platelet-Derived Growth Factor; C430456:desmuslin