Glutamatergic mechanisms in the dyskinesias induced by pharmacological dopamine replacement and deep brain stimulation for the treatment of Parkinson's disease
Sgambato-Faure, Veronique and Cenci Nilsson, Angela LU
(2012)
In Progress in Neurobiology
96(1).
p.69-86
- Abstract
- Dyskinesias represent a major complication of dopamine replacement therapy in Parkinson's disease (PD) and have prompted a search for alternative treatments. The most radical advances in this field have been provided by surgical manipulations of the deep basal ganglia nuclei, and particularly by deep brain stimulation (DBS) of the subthalamic nucleus (STN). Although being very effective, high-frequency stimulation (HFS) of the STN is a poorly understood treatment. Besides its anti-akinetic activity, it can be pro-dyskinetic above a certain stimulation intensity. Accumulating evidence indicates that dyskinesias induced by STN-HFS and dopamine replacement therapy are linked to dysregulation of glutamate transmission in the basal ganglia. In... (More)
- Dyskinesias represent a major complication of dopamine replacement therapy in Parkinson's disease (PD) and have prompted a search for alternative treatments. The most radical advances in this field have been provided by surgical manipulations of the deep basal ganglia nuclei, and particularly by deep brain stimulation (DBS) of the subthalamic nucleus (STN). Although being very effective, high-frequency stimulation (HFS) of the STN is a poorly understood treatment. Besides its anti-akinetic activity, it can be pro-dyskinetic above a certain stimulation intensity. Accumulating evidence indicates that dyskinesias induced by STN-HFS and dopamine replacement therapy are linked to dysregulation of glutamate transmission in the basal ganglia. In rat models of PD, both types of dyskinesia are associated with increased concentrations of extracellular glutamate and altered expression of glutamate transporters in the substantia nigra pars reticulata and the striatum. Furthermore, a vast and ever growing literature has revealed changes in the expression, phosphorylation state, and/or subcellular distribution of specific subtypes of glutamate receptors in these dyskinetic conditions. Both types of dyskinesias are linked to an increased phosphorylation of NR2B-containing NMDA receptors in critical basal ganglia circuits. We conclude that disruption of glutamate homeostasis and activation of perisynaptic and extra-synaptic glutamate receptors are an important pathophysiological component of these treatment-induced dyskinesias in PD. These findings lay the ground for therapeutic development initiatives targeting dysfunctional components of glutamate transmission in the basal ganglia. (C) 2011 Elsevier Ltd. All rights reserved. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2515913
- author
- Sgambato-Faure, Veronique
and Cenci Nilsson, Angela
LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- localization, Subcellular, Animal models, Metabotropic glutamate receptors, receptors, AMPA, Gliotransmission, NMDA receptors, Globus, pallidus, Neurotransmission, L-DOPA, Motor complications, High-frequency stimulation
- in
- Progress in Neurobiology
- volume
- 96
- issue
- 1
- pages
- 69 - 86
- publisher
- Elsevier
- external identifiers
-
- wos:000301210800004
- scopus:82955189290
- pmid:22075179
- ISSN
- 1873-5118
- DOI
- 10.1016/j.pneurobio.2011.10.005
- language
- English
- LU publication?
- yes
- id
- 68e42f6e-f67f-47ca-90b5-e307b6c73b6c (old id 2515913)
- date added to LUP
- 2016-04-01 10:55:22
- date last changed
- 2022-05-18 03:10:19
@article{68e42f6e-f67f-47ca-90b5-e307b6c73b6c,
abstract = {{Dyskinesias represent a major complication of dopamine replacement therapy in Parkinson's disease (PD) and have prompted a search for alternative treatments. The most radical advances in this field have been provided by surgical manipulations of the deep basal ganglia nuclei, and particularly by deep brain stimulation (DBS) of the subthalamic nucleus (STN). Although being very effective, high-frequency stimulation (HFS) of the STN is a poorly understood treatment. Besides its anti-akinetic activity, it can be pro-dyskinetic above a certain stimulation intensity. Accumulating evidence indicates that dyskinesias induced by STN-HFS and dopamine replacement therapy are linked to dysregulation of glutamate transmission in the basal ganglia. In rat models of PD, both types of dyskinesia are associated with increased concentrations of extracellular glutamate and altered expression of glutamate transporters in the substantia nigra pars reticulata and the striatum. Furthermore, a vast and ever growing literature has revealed changes in the expression, phosphorylation state, and/or subcellular distribution of specific subtypes of glutamate receptors in these dyskinetic conditions. Both types of dyskinesias are linked to an increased phosphorylation of NR2B-containing NMDA receptors in critical basal ganglia circuits. We conclude that disruption of glutamate homeostasis and activation of perisynaptic and extra-synaptic glutamate receptors are an important pathophysiological component of these treatment-induced dyskinesias in PD. These findings lay the ground for therapeutic development initiatives targeting dysfunctional components of glutamate transmission in the basal ganglia. (C) 2011 Elsevier Ltd. All rights reserved.}},
author = {{Sgambato-Faure, Veronique and Cenci Nilsson, Angela}},
issn = {{1873-5118}},
keywords = {{localization; Subcellular; Animal models; Metabotropic glutamate receptors; receptors; AMPA; Gliotransmission; NMDA receptors; Globus; pallidus; Neurotransmission; L-DOPA; Motor complications; High-frequency stimulation}},
language = {{eng}},
number = {{1}},
pages = {{69--86}},
publisher = {{Elsevier}},
series = {{Progress in Neurobiology}},
title = {{Glutamatergic mechanisms in the dyskinesias induced by pharmacological dopamine replacement and deep brain stimulation for the treatment of Parkinson's disease}},
url = {{http://dx.doi.org/10.1016/j.pneurobio.2011.10.005}},
doi = {{10.1016/j.pneurobio.2011.10.005}},
volume = {{96}},
year = {{2012}},
}