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, 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. [Display omitted] •MPP+ treatment activates the Nrf2 transcription factor in dopaminergic SK-N-BE neuroblastoma cells committed to die.•MPTP treatment induces Nrf2 transcription in substantia nigra pc area of mouse brain before the neurodegeneration onset.•Nrf2 signaling is an early marker of neurodegeneration, anticipating dopaminergic neurodegeneration.•In vivo bioluminescence imaging can be applied to study the molecular events occurring during the onset of brain diseases.