| 1. |
- Cenci Nilsson, Angela
(författare)
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L-DOPA-induced dyskinesia: cellular mechanisms and approaches to treatment.
- 2007
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Ingår i: Parkinsonism & Related Disorders. - 1873-5126. ; 13 Suppl 3, s. 263-267
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Tidskriftsartikel (refereegranskat)abstract
- L-DOPA-induced dyskinesia (LID) is a common complication of the treatment of Parkinson's disease, and its precise mechanisms have long remained unknown. Rodent models of LID provide a tool to dissect the impact of specific factors on the development and expression of dyskinetic movements. This short review will summarize recent findings from rodent studies that have consolidated and considerably expanded our mechanistic understanding of LID. Based on the experimental findings, the review will propose a chart of possible treatment options acting on different pathophysiological levels.
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| 2. |
- Cenci Nilsson, Angela, et al.
(författare)
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Plastic effects of L-DOPA treatment in the basal ganglia and their relevance to the development of dyskinesia.
- 2009
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Ingår i: Parkinsonism & Related Disorders. - 1873-5126. ; 15 Suppl 3, s. 59-63
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Tidskriftsartikel (refereegranskat)abstract
- The development of L-DOPA-induced dyskinesia (LID) is attributed to plastic responses triggered by dopamine (DA) receptor stimulation in the parkinsonian brain. This article reviews studies that have uncovered different levels of maladaptive plasticity in animal models of LID. Rats developing dyskinesia on chronic L-DOPA treatment show abnormal patterns of signaling pathway activation and synaptic plasticity in striatal neurons. In addition, these animals show a gene expression profile indicative of structural cellular plasticity, including pronounced upregulation of genes involved in extracellular matrix remodeling, neurite extension, synaptic vesicle trafficking, and endothelial and cellular proliferation. Structural changes of neurons and microvessels within the basal ganglia are currently being unraveled by detailed morphological analyses. The structural and functional adaptations induced by L-DOPA in the brain can be viewed as an attempt to meet increased metabolic demands and to boost cellular defense mechanisms. These homeostatic responses, however, also predispose to the appearance of dyskinesia and other complications during the course of the treatment.
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| 3. |
- Cenci Nilsson, Angela, et al.
(författare)
-
Rodent models of treatment-induced motor complications in Parkinson's disease
- 2009
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Ingår i: Parkinsonism and Related Disorders. - 1873-5126. ; 15 Suppl 4, s. 7-13
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Tidskriftsartikel (refereegranskat)abstract
- Treatment-induced motor complications represent a major clinical problem in Parkinson's disease (PD). Pharmacological dopamine (DA) replacement with l-dopa causes motor fluctuations and abnormal involuntary movements (dyskinesia) in the vast majority of the patients. Intrastriatal grafts of embryonic dopaminergic neurons can cause dyskinesia too, as shown by clinical trials of neural transplantation in PD. Animals models of these complications can be produced in rats and mice in which the nigrostriatal DA pathway has been severely damaged. Rodent models allow investigators to explore mechanistic hypotheses at the cellular and molecular level. Moreover, the rat model of L-dopa-induced abnormal involuntary movements shows both face validity and predictive validity relative to the corresponding disorder in primates, and provides a cost effective tool to evaluate novel antidyskinetic interventions. This article reviews the strategies that have been used to reproduce different motor complications of PD treatment in rodents, and comments on their range of applicability.
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