Pyrylium Based Derivatization Imaging Mass Spectrometer Revealed the Localization of L-DOPA

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2022 Aug 2

PMID 35917331

Authors

Shu Taira

Akari Ikeda

Yuki Sugiura

Hitomi Shikano

Shoko Kobayashi

Tsutomu Terauchi

Jun Yokoyama

Affiliations

Soon will be listed here.

Abstract

Simultaneous imaging of l-dihydroxyphenylalanine (l-DOPA), dopamine (DA) and norepinephrine (NE) in the catecholamine metabolic pathway is particularly useful because l-DOPA is a neurophysiologically important metabolic intermediate. In this study, we found that 2,4,6-trimethylpyrillium tetrafluoroborate (TMPy) can selectively and efficiently react with target catecholamine molecules. Specifically, simultaneous visualization of DA and NE as metabolites of l-DOPA with high steric hinderance was achieved by derivatized-imaging mass spectrometry (IMS). Interestingly, l-DOPA showed strong localization in the brainstem, in contrast to the pattern of DA and NE, which co-localized with tyrosine hydroxylase (TH). In addition, to identify whether the detected molecules were endogenous or exogenous l-DOPA, mice were injected with l-DOPA deuterated in three positions (D3-l-DOPA), which was identifiable by a mass shift of 3Da. TMPy-labeled l-DOPA, DA and NE were detected at m/z 302.1, 258.1 and 274.1, while their D3 versions were detected at 305.0, 261.1 and 277.1 in mouse brain, respectively. l-DOPA and D3-l-DOPA were localized in the BS. DA and NE, and D3-DA and D3-NE, all of which are metabolites of L-DOPA and D3-l-DOPA, were localized in the striatum (STR) and locus coeruleus (LC). These findings suggest a mechanism in the brainstem that allows l-DOPA to accumulate without being metabolized to monoamines downstream of the metabolic pathway.

Citing Articles

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References

Tatsuta Y, Tanaka Y, Ikeda A, Matsukawa S, Katano H, Taira S . Nanoparticle-Assisted Laser Desorption/Ionization Mass Spectrometry (Nano-PALDI MS) with Py-Tag for the Analysis of Small Molecules. Mass Spectrom (Tokyo). 2017; 6(Spec Iss 2):S0069. PMC: 5603941. DOI: 10.5702/massspectrometry.S0069. View

Subramanian N, Srimany A, Kanwar J, Kanwar R, Akilandeswari B, Rishi P . Nucleolin-aptamer therapy in retinoblastoma: molecular changes and mass spectrometry-based imaging. Mol Ther Nucleic Acids. 2016; 5(8):e358. PMC: 5023409. DOI: 10.1038/mtna.2016.70. View

Taira S, Sugiura Y, Moritake S, Shimma S, Ichiyanagi Y, Setou M . Nanoparticle-assisted laser desorption/ionization based mass imaging with cellular resolution. Anal Chem. 2008; 80(12):4761-6. DOI: 10.1021/ac800081z. View

Callicott J, Ramsey N, Tallent K, Bertolino A, Knable M, Coppola R . Functional magnetic resonance imaging brain mapping in psychiatry: methodological issues illustrated in a study of working memory in schizophrenia. Neuropsychopharmacology. 1998; 18(3):186-96. DOI: 10.1016/S0893-133X(97)00096-1. View

Shiota M, Shimomura Y, Kotera M, Taira S . Mass spectrometric imaging of localization of fat molecules in water-in-oil emulsions containing semi-solid fat. Food Chem. 2017; 245:1218-1223. DOI: 10.1016/j.foodchem.2017.11.009. View

Esteve C, Tolner E, Shyti R, van den Maagdenberg A, McDonnell L . Mass spectrometry imaging of amino neurotransmitters: a comparison of derivatization methods and application in mouse brain tissue. Metabolomics. 2016; 12:30. PMC: 4705126. DOI: 10.1007/s11306-015-0926-0. View

Huang L, Tang X, Zhang W, Jiang R, Chen D, Zhang J . Imaging of Endogenous Metabolites of Plant Leaves by Mass Spectrometry Based on Laser Activated Electron Tunneling. Sci Rep. 2016; 6:24164. PMC: 4823709. DOI: 10.1038/srep24164. View

Gittis A, Kreitzer A . Striatal microcircuitry and movement disorders. Trends Neurosci. 2012; 35(9):557-64. PMC: 3432144. DOI: 10.1016/j.tins.2012.06.008. View

Steinhauser M, Bailey A, Senyo S, Guillermier C, Perlstein T, Gould A . Multi-isotope imaging mass spectrometry quantifies stem cell division and metabolism. Nature. 2012; 481(7382):516-9. PMC: 3267887. DOI: 10.1038/nature10734. View

10.

Sugiura Y, Taguchi R, Setou M . Visualization of spatiotemporal energy dynamics of hippocampal neurons by mass spectrometry during a kainate-induced seizure. PLoS One. 2011; 6(3):e17952. PMC: 3062556. DOI: 10.1371/journal.pone.0017952. View

11.

Tatsuta Y, Kasai K, Maruyama C, Hamano Y, Matsuo K, Katano H . Imaging mass spectrometry analysis of ubiquinol localization in the mouse brain following short-term administration. Sci Rep. 2017; 7(1):12990. PMC: 5636788. DOI: 10.1038/s41598-017-13257-8. View

12.

Nissbrandt H, Engberg G, Wikstrom H, Magnusson T, Carlsson A . NSD 1034: an amino acid decarboxylase inhibitor with a stimulatory action on dopamine synthesis not mediated by classical dopamine receptors. Naunyn Schmiedebergs Arch Pharmacol. 1988; 338(2):148-61. DOI: 10.1007/BF00174863. View

13.

Xenias H, Ibanez-Sandoval O, Koos T, Tepper J . Are striatal tyrosine hydroxylase interneurons dopaminergic?. J Neurosci. 2015; 35(16):6584-99. PMC: 4405564. DOI: 10.1523/JNEUROSCI.0195-15.2015. View

14.

Shariatgorji M, Strittmatter N, Nilsson A, Kallback P, Alvarsson A, Zhang X . Simultaneous imaging of multiple neurotransmitters and neuroactive substances in the brain by desorption electrospray ionization mass spectrometry. Neuroimage. 2016; 136:129-38. DOI: 10.1016/j.neuroimage.2016.05.004. View

15.

Taira S, Ikeda R, Yokota N, Osaka I, Sakamoto M, Kato M . Mass spectrometric imaging of ginsenosides localization in Panax ginseng root. Am J Chin Med. 2010; 38(3):485-93. DOI: 10.1142/S0192415X10008007. View

16.

Andersen A, Blaabjerg M, Binzer M, Kamal A, Thagesen H, Kjaer T . Cerebrospinal fluid levels of catecholamines and its metabolites in Parkinson's disease: effect of l-DOPA treatment and changes in levodopa-induced dyskinesia. J Neurochem. 2017; 141(4):614-625. DOI: 10.1111/jnc.13997. View

17.

Hase T, Shishido S, Yamamoto S, Yamashita R, Nukima H, Taira S . Rosmarinic acid suppresses Alzheimer's disease development by reducing amyloid β aggregation by increasing monoamine secretion. Sci Rep. 2019; 9(1):8711. PMC: 6581955. DOI: 10.1038/s41598-019-45168-1. View

18.

Kvetnansky R, Sabban E, Palkovits M . Catecholaminergic systems in stress: structural and molecular genetic approaches. Physiol Rev. 2009; 89(2):535-606. DOI: 10.1152/physrev.00042.2006. View

19.

Lieberman H, Thompson L, Caruso C, Niro P, Mahoney C, McClung J . The catecholamine neurotransmitter precursor tyrosine increases anger during exposure to severe psychological stress. Psychopharmacology (Berl). 2014; 232(5):943-51. PMC: 4325185. DOI: 10.1007/s00213-014-3727-7. View

20.

Friedman J, Adler D, Davis K . The role of norepinephrine in the pathophysiology of cognitive disorders: potential applications to the treatment of cognitive dysfunction in schizophrenia and Alzheimer's disease. Biol Psychiatry. 1999; 46(9):1243-52. DOI: 10.1016/s0006-3223(99)00232-2. View