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Brain Morphometry and the Neurobiology of Levodopa-Induced Dyskinesias: Current Knowledge and Future Potential for Translational Pre-Clinical Neuroimaging Studies
Dopamine replacement therapy in the form of levodopa results in a significant proportion of patients with Parkinson’s disease developing debilitating dyskinesia. This significantly complicates further treatment and negatively impacts patient quality of life. A greater understanding of the neurobiolo...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053925/ https://www.ncbi.nlm.nih.gov/pubmed/24971074 http://dx.doi.org/10.3389/fneur.2014.00095 |
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author | Finlay, Clare J. Duty, Susan Vernon, Anthony C. |
author_facet | Finlay, Clare J. Duty, Susan Vernon, Anthony C. |
author_sort | Finlay, Clare J. |
collection | PubMed |
description | Dopamine replacement therapy in the form of levodopa results in a significant proportion of patients with Parkinson’s disease developing debilitating dyskinesia. This significantly complicates further treatment and negatively impacts patient quality of life. A greater understanding of the neurobiological mechanisms underlying levodopa-induced dyskinesia (LID) is therefore crucial to develop new treatments to prevent or mitigate LID. Such investigations in humans are largely confined to assessment of neurochemical and cerebrovascular blood flow changes using positron emission tomography and functional magnetic resonance imaging. However, recent evidence suggests that LID is associated with specific morphological changes in the frontal cortex and midbrain, detectable by structural MRI and voxel-based morphometry. Current human neuroimaging methods however lack sufficient resolution to reveal the biological mechanism driving these morphological changes at the cellular level. In contrast, there is a wealth of literature from well-established rodent models of LID documenting detailed post-mortem cellular and molecular measurements. The combination therefore of advanced neuroimaging methods and rodent LID models offers an exciting opportunity to bridge these currently disparate areas of research. To highlight this opportunity, in this mini-review, we provide an overview of the current clinical evidence for morphological changes in the brain associated with LID and identify potential cellular mechanisms as suggested from human and animal studies. We then suggest a framework for combining small animal MRI imaging with rodent models of LID, which may provide important mechanistic insights into the neurobiology of LID. |
format | Online Article Text |
id | pubmed-4053925 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-40539252014-06-26 Brain Morphometry and the Neurobiology of Levodopa-Induced Dyskinesias: Current Knowledge and Future Potential for Translational Pre-Clinical Neuroimaging Studies Finlay, Clare J. Duty, Susan Vernon, Anthony C. Front Neurol Neuroscience Dopamine replacement therapy in the form of levodopa results in a significant proportion of patients with Parkinson’s disease developing debilitating dyskinesia. This significantly complicates further treatment and negatively impacts patient quality of life. A greater understanding of the neurobiological mechanisms underlying levodopa-induced dyskinesia (LID) is therefore crucial to develop new treatments to prevent or mitigate LID. Such investigations in humans are largely confined to assessment of neurochemical and cerebrovascular blood flow changes using positron emission tomography and functional magnetic resonance imaging. However, recent evidence suggests that LID is associated with specific morphological changes in the frontal cortex and midbrain, detectable by structural MRI and voxel-based morphometry. Current human neuroimaging methods however lack sufficient resolution to reveal the biological mechanism driving these morphological changes at the cellular level. In contrast, there is a wealth of literature from well-established rodent models of LID documenting detailed post-mortem cellular and molecular measurements. The combination therefore of advanced neuroimaging methods and rodent LID models offers an exciting opportunity to bridge these currently disparate areas of research. To highlight this opportunity, in this mini-review, we provide an overview of the current clinical evidence for morphological changes in the brain associated with LID and identify potential cellular mechanisms as suggested from human and animal studies. We then suggest a framework for combining small animal MRI imaging with rodent models of LID, which may provide important mechanistic insights into the neurobiology of LID. Frontiers Media S.A. 2014-06-12 /pmc/articles/PMC4053925/ /pubmed/24971074 http://dx.doi.org/10.3389/fneur.2014.00095 Text en Copyright © 2014 Finlay, Duty and Vernon. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Finlay, Clare J. Duty, Susan Vernon, Anthony C. Brain Morphometry and the Neurobiology of Levodopa-Induced Dyskinesias: Current Knowledge and Future Potential for Translational Pre-Clinical Neuroimaging Studies |
title | Brain Morphometry and the Neurobiology of Levodopa-Induced Dyskinesias: Current Knowledge and Future Potential for Translational Pre-Clinical Neuroimaging Studies |
title_full | Brain Morphometry and the Neurobiology of Levodopa-Induced Dyskinesias: Current Knowledge and Future Potential for Translational Pre-Clinical Neuroimaging Studies |
title_fullStr | Brain Morphometry and the Neurobiology of Levodopa-Induced Dyskinesias: Current Knowledge and Future Potential for Translational Pre-Clinical Neuroimaging Studies |
title_full_unstemmed | Brain Morphometry and the Neurobiology of Levodopa-Induced Dyskinesias: Current Knowledge and Future Potential for Translational Pre-Clinical Neuroimaging Studies |
title_short | Brain Morphometry and the Neurobiology of Levodopa-Induced Dyskinesias: Current Knowledge and Future Potential for Translational Pre-Clinical Neuroimaging Studies |
title_sort | brain morphometry and the neurobiology of levodopa-induced dyskinesias: current knowledge and future potential for translational pre-clinical neuroimaging studies |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053925/ https://www.ncbi.nlm.nih.gov/pubmed/24971074 http://dx.doi.org/10.3389/fneur.2014.00095 |
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