Simultaneous mass spectrometry imaging of multiple neuropeptides in the brain and alterations induced by experimental parkinsonism and L-DOPA therapy.

Abstract

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 evaluated 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 a unilateral 6-hydroxydopamine rat model of Parkinson's disease, 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.

• Authors: Heather Hulme, Elva Fridjonsdottir, Halla Gunnarsdottir, Theodosia Vallianatou, Xiaoqun Zhang, Henrik Wadensten, Reza Shariatgorji, Anna Nilsson, Erwan Bezard, Per Svenningsson, Per E Andrén
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 137 Pg. 104738 (04 2020) ISSN: 1095-953X [Electronic] United States
• PMID: 31927144 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Enkephalins
• Levodopa
• Dynorphins

Topics

• Animals
• Brain (drug effects, metabolism)
• Dynorphins (metabolism)
• Dyskinesia, Drug-Induced (metabolism)
• Enkephalins (metabolism)
• Globus Pallidus (metabolism)
• Levodopa (pharmacology)
• Male
• Neostriatum (drug effects, metabolism)
• Parkinsonian Disorders (drug therapy, metabolism)
• Rats, Wistar