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Mass spectrometry imaging of multiple basal ganglia neuropeptides shows abnormal neuropeptide processing associated with L-DOPA-induced dyskinesia in a primate model of Parkinson’s disease
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- Hulme, Heather (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab,Medical mass spectrometry imaging
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- Fridjonsdottir, Elva (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Medical mass spectrometry imaging
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- Vallianatou, Theodosia (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Medical mass spectrometry imaging
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visa fler...
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- Shariatgorji, Mohammadreza (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab,Medical mass spectrometry imaging
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- Nilsson, Anna (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab,Medical mass spectrometry imaging
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- Li, Qin (författare)
- Motac Neuroscience, Manchester, M15 6WE, UK
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- Bezard, Erwan (författare)
- Motac Neuroscience, Manchester, M15 6WE, United Kingdom. Université de Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux, France. Centre National de la Recherche Scientifique, Institut des Maladies Neurodégénératives, Bordeaux, France
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- Andrén, Per E., Professor, 1957- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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visa färre...
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(creator_code:org_t)
- Engelska.
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- L-DOPA administration is the primary treatment for Parkinson’s disease (PD) but long-term administration is usually accompanied by hyperkinetic side-effects called L-DOPA-induced dyskinesia (LID). Signalling neuropeptides of the basal ganglia are affected in LID and alterations in the expression of neuropeptide precursors have been described, but the final products of the precursors are not well defined and regionally mapped. Thus, we used matrix-assisted laser desorption/ionization mass spectrometry imaging to visualize and quantify neuropeptides in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposed parkinsonian and LID Macaca mulatta brain samples. We found that the abundance of some abnormally processed peptides—des-tyrosine dynorphins, substance P (1-7) and substance P (1-9)—correlated with dyskinesia severity in multiple brain regions. Other dynorphins, α-neoendorphin and neurokinin A correlated with regional L-DOPA or dopamine levels in the internal and external globus pallidus. Our results demonstrate that the abundance of selected active neuropeptides is associated with local L-DOPA and dopamine concentrations, but the severity of LID is associated with loss of N-terminal tyrosine from dynorphin peptides and C-terminal truncation of substance P peptides, modifications that generally reduce the neuropeptides’ activity.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- NATURVETENSKAP -- Kemi -- Analytisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Analytical Chemistry (hsv//eng)
Nyckelord
- Neuropeptides
- Parkinson's disease
- L-DOPA-induced dyskinesia
- MALDI
- Mass spectrometry imaging
- Farmaceutisk vetenskap
- Pharmaceutical Science
- Patologi
- Pathology
Publikations- och innehållstyp
- vet (ämneskategori)
- ovr (ämneskategori)