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Dopamine Transporter/α-Synuclein Complexes Are Altered in the Post Mortem Caudate Putamen of Parkinson’s Disease: An In Situ Proximity Ligation Assay Study

1
Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
2
Laboratory of Personalized and Preventive Medicine, University of Brescia, 25123 Brescia, Italy
*
Author to whom correspondence should be addressed.
Division of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa No. 11, 25123 Brescia, Italy.
Int. J. Mol. Sci. 2018, 19(6), 1611; https://doi.org/10.3390/ijms19061611
Received: 23 April 2018 / Revised: 21 May 2018 / Accepted: 26 May 2018 / Published: 30 May 2018
(This article belongs to the Special Issue Molecular Research on Neurodegenerative Diseases)
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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. View Full-Text
Keywords: dopamine transporter; α-synuclein; Parkinson’s disease; proximity ligation assay dopamine transporter; α-synuclein; Parkinson’s disease; proximity ligation assay
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Longhena, F.; Faustini, G.; Missale, C.; Pizzi, M.; Bellucci, A. Dopamine Transporter/α-Synuclein Complexes Are Altered in the Post Mortem Caudate Putamen of Parkinson’s Disease: An In Situ Proximity Ligation Assay Study. Int. J. Mol. Sci. 2018, 19, 1611.

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