In vivo imaging of early signs of dopaminergic neuronal death in an animal model of Parkinson's disease
The Parkinson's disease (PD) evolves over an extended period of time with the onset occurring long before clinical signs begin to manifest. Characterization of the molecular events underlying the PD onset is instrumental for the development of diagnostic markers and preventive treatments, progr...
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doaj-8c68cfc48c834a86be085fb7f2b50b662021-03-22T12:46:17ZengElsevierNeurobiology of Disease1095-953X2018-06-011147484In vivo imaging of early signs of dopaminergic neuronal death in an animal model of Parkinson's diseaseNicoletta Rizzi0Electra Brunialti1Silvia Cerri2Greta Cermisoni3Giovanna Levandis4Nicoletta Cesari5Adriana Maggi6Fabio Blandini7Paolo Ciana8Center of Excellence for Neurodegenerative Diseases, Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, ItalyCenter of Excellence for Neurodegenerative Diseases, Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, ItalyLaboratory of Functional Neurochemistry, IRCCS Mondino Foundation, via Mondino 2, 27100 Pavia, Pavia, ItalyCenter of Excellence for Neurodegenerative Diseases, Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, ItalyLaboratory of Functional Neurochemistry, IRCCS Mondino Foundation, via Mondino 2, 27100 Pavia, Pavia, ItalyCentro Clinico-Veterinario e Zootecnico-Sperimentale d'Ateneo, University of Milan, Via dell'Università 6, 26900 Lodi, ItalyCenter of Excellence for Neurodegenerative Diseases, Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, ItalyLaboratory of Functional Neurochemistry, IRCCS Mondino Foundation, via Mondino 2, 27100 Pavia, Pavia, ItalyCenter of Excellence for Neurodegenerative Diseases, Department of Oncology and Hemato-Oncology, University of Milan, Via Balzaretti 9, 20133 Milan, Italy; Corresponding author.The Parkinson's disease (PD) evolves over an extended period of time with the onset occurring long before clinical signs begin to manifest. Characterization of the molecular events underlying the PD onset is instrumental for the development of diagnostic markers and preventive treatments, progress in this field is hindered by technical limitations. We applied an imaging approach to demonstrate the activation of Nrf2 transcription factor as a hallmark of neurodegeneration in neurotoxin-driven models of PD. In dopaminergic SK-N-BE neuroblastoma cells, Nrf2 activation was detected in cells committed to die as proven by time lapse microscopy; in the substantia nigra pars compacta area of the mouse brain, the Nrf2 activation preceded dopaminergic neurodegeneration as demonstrated by in vivo and ex vivo optical imaging, a finding confirmed by co-localization experiments carried out by immunohistochemistry. Collectively, our results identify the Nrf2 signaling as an early marker of neurodegeneration, anticipating dopaminergic neurodegeneration and motor deficits.http://www.sciencedirect.com/science/article/pii/S0969996118300378Nrf-2Reporter mouseBioluminescenceIn vivo imagingParkinson's diseaseAnti-oxidant responsive elements |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nicoletta Rizzi Electra Brunialti Silvia Cerri Greta Cermisoni Giovanna Levandis Nicoletta Cesari Adriana Maggi Fabio Blandini Paolo Ciana |
spellingShingle |
Nicoletta Rizzi Electra Brunialti Silvia Cerri Greta Cermisoni Giovanna Levandis Nicoletta Cesari Adriana Maggi Fabio Blandini Paolo Ciana In vivo imaging of early signs of dopaminergic neuronal death in an animal model of Parkinson's disease Neurobiology of Disease Nrf-2 Reporter mouse Bioluminescence In vivo imaging Parkinson's disease Anti-oxidant responsive elements |
author_facet |
Nicoletta Rizzi Electra Brunialti Silvia Cerri Greta Cermisoni Giovanna Levandis Nicoletta Cesari Adriana Maggi Fabio Blandini Paolo Ciana |
author_sort |
Nicoletta Rizzi |
title |
In vivo imaging of early signs of dopaminergic neuronal death in an animal model of Parkinson's disease |
title_short |
In vivo imaging of early signs of dopaminergic neuronal death in an animal model of Parkinson's disease |
title_full |
In vivo imaging of early signs of dopaminergic neuronal death in an animal model of Parkinson's disease |
title_fullStr |
In vivo imaging of early signs of dopaminergic neuronal death in an animal model of Parkinson's disease |
title_full_unstemmed |
In vivo imaging of early signs of dopaminergic neuronal death in an animal model of Parkinson's disease |
title_sort |
in vivo imaging of early signs of dopaminergic neuronal death in an animal model of parkinson's disease |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2018-06-01 |
description |
The Parkinson's disease (PD) evolves over an extended period of time with the onset occurring long before clinical signs begin to manifest. Characterization of the molecular events underlying the PD onset is instrumental for the development of diagnostic markers and preventive treatments, progress in this field is hindered by technical limitations. We applied an imaging approach to demonstrate the activation of Nrf2 transcription factor as a hallmark of neurodegeneration in neurotoxin-driven models of PD. In dopaminergic SK-N-BE neuroblastoma cells, Nrf2 activation was detected in cells committed to die as proven by time lapse microscopy; in the substantia nigra pars compacta area of the mouse brain, the Nrf2 activation preceded dopaminergic neurodegeneration as demonstrated by in vivo and ex vivo optical imaging, a finding confirmed by co-localization experiments carried out by immunohistochemistry. Collectively, our results identify the Nrf2 signaling as an early marker of neurodegeneration, anticipating dopaminergic neurodegeneration and motor deficits. |
topic |
Nrf-2 Reporter mouse Bioluminescence In vivo imaging Parkinson's disease Anti-oxidant responsive elements |
url |
http://www.sciencedirect.com/science/article/pii/S0969996118300378 |
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