Time course and progression of wild type α-Synuclein accumulation in a transgenic mouse model
<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...
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doaj-8e41c919872147e196633664c57597ac2020-11-24T22:06:26ZengBMCBMC Neuroscience1471-22022013-01-01141610.1186/1471-2202-14-6Time course and progression of wild type α-Synuclein accumulation in a transgenic mouse modelAmschl DavidNeddens JörgHavas DanielFlunkert StefanieRabl RolandRömer HeinrichRockenstein EdwardMasliah EliezerWindisch ManfredHutter-Paier Birgit<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> http://www.biomedcentral.com/1471-2202/14/6BehaviorImmunofluorescenceMotor deficitMouse modelParkinson’s diseasePhosphorylationSynucleinopathyα-SynucleinTransgene |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Amschl David Neddens Jörg Havas Daniel Flunkert Stefanie Rabl Roland Römer Heinrich Rockenstein Edward Masliah Eliezer Windisch Manfred Hutter-Paier Birgit |
spellingShingle |
Amschl David Neddens Jörg Havas Daniel Flunkert Stefanie Rabl Roland Römer Heinrich Rockenstein Edward Masliah Eliezer Windisch Manfred Hutter-Paier Birgit Time course and progression of wild type α-Synuclein accumulation in a transgenic mouse model BMC Neuroscience Behavior Immunofluorescence Motor deficit Mouse model Parkinson’s disease Phosphorylation Synucleinopathy α-Synuclein Transgene |
author_facet |
Amschl David Neddens Jörg Havas Daniel Flunkert Stefanie Rabl Roland Römer Heinrich Rockenstein Edward Masliah Eliezer Windisch Manfred Hutter-Paier Birgit |
author_sort |
Amschl David |
title |
Time course and progression of wild type α-Synuclein accumulation in a transgenic mouse model |
title_short |
Time course and progression of wild type α-Synuclein accumulation in a transgenic mouse model |
title_full |
Time course and progression of wild type α-Synuclein accumulation in a transgenic mouse model |
title_fullStr |
Time course and progression of wild type α-Synuclein accumulation in a transgenic mouse model |
title_full_unstemmed |
Time course and progression of wild type α-Synuclein accumulation in a transgenic mouse model |
title_sort |
time course and progression of wild type α-synuclein accumulation in a transgenic mouse model |
publisher |
BMC |
series |
BMC Neuroscience |
issn |
1471-2202 |
publishDate |
2013-01-01 |
description |
<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> |
topic |
Behavior Immunofluorescence Motor deficit Mouse model Parkinson’s disease Phosphorylation Synucleinopathy α-Synuclein Transgene |
url |
http://www.biomedcentral.com/1471-2202/14/6 |
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