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

Publication date: Jan 09, 2020

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-ionization 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.

Hulme, H., Fridjonsdottir, E., Gunnarsdottir, H., Vallianatou, T., Zhang, X., Wadensten, H., Shariatgorji, R., Nilsson, A., Bezard, E., Svenningsson, P., and Andr’en, P.E. Simultaneous mass spectrometry imaging of multiple neuropeptides in the brain and alterations induced by experimental parkinsonism and L-DOPA therapy. 23623. 2020 Neurobiol Dis.

Concepts Keywords
Brain Enkephalin
Caudate Putamen Dopa
Desorption Biochemistry
DOPA Neuropeptide
Dopamine Catecholamines
Dopaminergic Molecular biology
Dorsal Branches of biology
Dynorphins Lateral resolution imaging
Enkephalins Spectrometry imaging
Globus Pallidus L-DOPA
Ionization Basal ganglia
Laser Neurotensin
Matrix Tyrosine hydroxylase
Neurological Disorders Laser
Neuropeptide
Neuropeptides
Neurotensin
Parkinson
Parkinsonism
Primate
Tachykinins

Semantics

Type Source Name
disease MESH multiple
drug DRUGBANK Levodopa
disease MESH neurological disorders
drug DRUGBANK Dopamine

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