Oral Presentation 25th Annual Lorne Proteomics Symposium 2020

Simultaneous mass spectrometry imaging of multiple neuropeptides in the brain and alterations induced by experimental Parkinsonism and L-DOPA therapy (#56)

Per E. Andren 1 , Heather Hulme 1 , Elva Fridjonsdottir 1 , Halla Gunnarsdottir 1 , Theodosia Vallianatou 1 , Xiaoqun Zhang 2 , Henrik Wadensten 1 , Reza Shariatgorji 1 , Anna Nilsson 1 , Erwan Bezard 3 , Per Svenningsson 2
  1. Dept. of Pharmaceutical Biosciences, Medical Mass Spectrometry Imaging, Uppsala University, Uppsala, Sweden
  2. Dept. of Neurology, Karolinska Institutet, Stockholm, Sweden
  3. Université de Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux, France

Neuropeptides are important signalling molecules in the brain and alterations in their expression levels have been linked to neurological disorders such as Parkinson’s disease. It is challenging to map neuropeptide changes across and within brain regions because of their low in vivo concentrations and complex post-translational processing. Consequently, the role of neuropeptides in Parkinson’s disease is not well understood. Thus, we have developed and validated a method to image multiple neuropeptides simultaneously in both rat and primate brain tissue sections by matrix-assisted laser desorption-ionisation mass spectrometry imaging at high lateral resolution. Using two neurotoxin models of Parkinson's disease, i.e., the unilateral 6-hydroxydopamine rat model and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model, we imaged changes in enkephalins, dynorphins, tachykinins and neurotensin associated with the dopaminergic denervation and L-DOPA treatment in multiple brain regions. L-DOPA administration significantly affected neuropeptides in the globus pallidus, while neuropeptides in the caudate-putamen were mostly affected by dopamine depletion. Using high lateral resolution imaging, we observed an increase of neurotensin in the dorsal sub-region of the globus pallidus after dopamine depletion. This study highlights the capacity of mass spectrometry imaging to elucidate the dynamics of neuropeptide signalling during Parkinson’s disease and its treatment.