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Basal ganglia neuro...
Basal ganglia neuropeptides show abnormal processing associated with L-DOPA-induced dyskinesia
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- Hulme, Heather (författare)
- Uppsala Univ, Dept Pharmaceut Biosci, Med Mass Spectrometry Imaging, Uppsala, Sweden.;Uppsala Univ, Sci Life Lab, Spatial Mass Spectrometry, Uppsala, Sweden.
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- Fridjonsdottir, Elva (författare)
- Uppsala Univ, Dept Pharmaceut Biosci, Med Mass Spectrometry Imaging, Uppsala, Sweden.
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- Vallianatou, Theodosia (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Shariatgorji, Reza (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Nilsson, Anna (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Li, Qin (författare)
- Motac Neurosci, Manchester M15 6WE, Lancs, England.
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- Bezard, Erwan (författare)
- Motac Neurosci, Manchester M15 6WE, Lancs, England.;Univ Bordeaux, Inst Malad Neurodegenerat, Bordeaux, France.;Ctr Natl Rech Sci, Inst Malad Neurodegenerat, Bordeaux, France.
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- Andrén, Per E., Professor, 1957- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Institutionen för läkemedelskemi,Science for Life Laboratory, SciLifeLab
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Uppsala Univ, Dept Pharmaceut Biosci, Med Mass Spectrometry Imaging, Uppsala, Sweden;Uppsala Univ, Sci Life Lab, Spatial Mass Spectrometry, Uppsala, Sweden. Uppsala Univ, Dept Pharmaceut Biosci, Med Mass Spectrometry Imaging, Uppsala, Sweden. (creator_code:org_t)
- 2022-04-13
- 2022
- Engelska.
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Ingår i: npj Parkinson's Disease. - : Springer Nature. - 2373-8057. ; 8:1
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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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). Signaling neuropeptides of the basal ganglia are affected in LID and changes in the expression of neuropeptide precursors have been described, but the final products formed from these precursors have not been well defined and regionally mapped. We therefore used 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 dyskinesia severity correlated with the levels of some abnormally processed peptides - notably, des-tyrosine dynorphins, substance P (1-7), and substance P (1-9) - in multiple brain regions. Levels of the active neuropeptides; dynorphin B, dynorphin A (1-8), alpha-neoendorphin, substance P (1-11), and neurokinin A, in the globus pallidus and substantia nigra correlated with putaminal levels of L-DOPA. Our results demonstrate that the abundance of selected active neuropeptides is associated with L-DOPA concentrations in the putamen, emphasizing their sensitivity to L-DOPA. Additionally, levels of truncated neuropeptides (which generally exhibit reduced or altered receptor affinity) correlate with dyskinesia severity, particularly for peptides associated with the direct pathway (i.e., dynorphins and tachykinins). The increases in tone of the tachykinin, enkephalin, and dynorphin neuropeptides in LID result in abnormal processing of neuropeptides with different biological activity and may constitute a functional compensatory mechanism for balancing the increased L-DOPA levels across the whole basal ganglia.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
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- ref (ämneskategori)
- art (ämneskategori)
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