Simultaneous mass spectrometry imaging of multiple neuropeptides in the brain and alterations induced by experimental parkinsonism and L-DOPA therapy.
Neurobiology of Disease. 2020-04-01; 137: 104738
DOI: 10.1016/j.nbd.2020.104738
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1. Neurobiol Dis. 2020 Apr;137:104738. doi: 10.1016/j.nbd.2020.104738. Epub 2020 Jan
10.
Simultaneous mass spectrometry imaging of multiple neuropeptides in the brain and
alterations induced by experimental parkinsonism and L-DOPA therapy.
Hulme H(1), Fridjonsdottir E(2), Gunnarsdottir H(2), Vallianatou T(2), Zhang
X(3), Wadensten H(2), Shariatgorji R(1), Nilsson A(1), Bezard E(4), Svenningsson
P(3), Andrén PE(5).
Author information:
(1)Medical Mass Spectrometry Imaging, Department of Pharmaceutical Biosciences,
Uppsala University, Uppsala, Sweden; Science for Life Laboratory, National
Resource for Mass Spectrometry Imaging, Uppsala University, Uppsala, Sweden.
(2)Medical Mass Spectrometry Imaging, Department of Pharmaceutical Biosciences,
Uppsala University, Uppsala, Sweden.
(3)Section of Neurology, Department of Clinical Neuroscience, Karolinska
Institutet, Stockholm, Sweden.
(4)Université de Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux,
France; Centre National de la Recherche Scientifique, Institut des Maladies
Neurodégénératives, Bordeaux, France.
(5)Medical Mass Spectrometry Imaging, Department of Pharmaceutical Biosciences,
Uppsala University, Uppsala, Sweden; Science for Life Laboratory, National
Resource for Mass Spectrometry Imaging, Uppsala University, Uppsala, Sweden.
Electronic address: .
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.
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
DOI: 10.1016/j.nbd.2020.104738
PMID: 31927144
Conflict of interest statement: Declaration of Competing Interest None.