Parkinson's disease (PD) is characterized by the degeneration of the dopaminergic nigrostriatal neurons and the presence of Lewy bodies (LB) and Lewy neurites (LN) mainly composed of α-synuclein. By using the in situ proximity ligation assay (PLA), which allows for the visualization of protein-protein interactions in tissues to detect dopamine transporter (DAT)/α-synuclein complexes, we previously described that these are markedly redistributed in the striatum of human α-synuclein transgenic mice at the phenotypic stage, showing dopamine (DA) release impairment without a DAT drop and motor symptoms. Here, we used the in situ PLA to investigate DAT/α-synuclein complexes in the caudate putamen of PD patients and age-matched controls. They were found to be redistributed and showed an increased size in PD patients, where we observed several neuropil-like and neuritic-like PLA-positive structures. In the PD brains, DAT immunolabeling showed a pattern similar to that of in situ PLA in areas with abundant α-synuclein neuropathology. This notwithstanding, the in situ PLA signal was only partially retracing DAT or α-synuclein immunolabeling, suggesting that a large amount of complexes may have been lost along with the degeneration process. These findings reveal a DAT/α-synuclein neuropathological signature in PD and hint that synaptic alterations involving striatal DAT may derive from α-synuclein aggregation.

Dopamine transporter/α-synuclein complexes are altered in the post mortem caudate putamen of Parkinson’s disease: An in situ proximity ligation assay study

Longhena, Francesca
Methodology
;
Faustini, Gaia
Methodology
;
Missale, Cristina
Writing – Review & Editing
;
Pizzi, Marina
Funding Acquisition
;
Bellucci, Arianna
Project Administration
2018-01-01

Abstract

Parkinson's disease (PD) is characterized by the degeneration of the dopaminergic nigrostriatal neurons and the presence of Lewy bodies (LB) and Lewy neurites (LN) mainly composed of α-synuclein. By using the in situ proximity ligation assay (PLA), which allows for the visualization of protein-protein interactions in tissues to detect dopamine transporter (DAT)/α-synuclein complexes, we previously described that these are markedly redistributed in the striatum of human α-synuclein transgenic mice at the phenotypic stage, showing dopamine (DA) release impairment without a DAT drop and motor symptoms. Here, we used the in situ PLA to investigate DAT/α-synuclein complexes in the caudate putamen of PD patients and age-matched controls. They were found to be redistributed and showed an increased size in PD patients, where we observed several neuropil-like and neuritic-like PLA-positive structures. In the PD brains, DAT immunolabeling showed a pattern similar to that of in situ PLA in areas with abundant α-synuclein neuropathology. This notwithstanding, the in situ PLA signal was only partially retracing DAT or α-synuclein immunolabeling, suggesting that a large amount of complexes may have been lost along with the degeneration process. These findings reveal a DAT/α-synuclein neuropathological signature in PD and hint that synaptic alterations involving striatal DAT may derive from α-synuclein aggregation.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11379/507862
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