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.

In vivo imaging of early signs of dopaminergic neuronal death in an animal model of Parkinson's disease / N. Rizzi, E. Brunialti, S. Cerri, G. Cermisoni, G. Levandis, N. Cesari, A. Maggi, F. Blandini, P. Ciana. - In: NEUROBIOLOGY OF DISEASE. - ISSN 0969-9961. - 114(2018 Jun), pp. 74-84. [10.1016/j.nbd.2018.02.005]

In vivo imaging of early signs of dopaminergic neuronal death in an animal model of Parkinson's disease

N. Rizzi;E. Brunialti;G. Cermisoni;A. Maggi;P. Ciana
2018-06

Abstract

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.
anti-oxidant responsive elements; ARE-luc2 mouse; bioluminescence; In vivo imaging; Nrf-2; oxidative stress; Parkinson's disease; reporter mouse; neurology
Settore BIO/14 - Farmacologia
24-feb-2018
NEUROBIOLOGY OF DISEASE
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/565418
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