L‐DOPA‐induced dyskinesia and neuroinflammation: do microglia and astrocytes play a role?. (9th December 2016)

• Record Type: Journal Article
• Authors: Carta, Anna R.; Mulas, Giovanna; Bortolanza, Mariza; Duarte, Terence; Pillai, Elisabetta; Fisone, Gilberto; Vozari, Rita Raisman; Del‐Bel, Elaine
• Editors: Bolam, Paul
• Is Part Of: European journal of neuroscience. Volume 45:Number 1(2017)
• Page Start: 73
• Page End: 91
• Publication Date: 2016-12-09
• Subjects: cytokine -- inducible nitric oxide synthase -- nitric oxide -- Parkinson's disease -- tumor necrosis factor‐α; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.13482
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: In Parkinson's disease (PD), l ‐DOPA therapy leads to the emergence of motor complications includingl ‐DOPA‐induced dyskinesia (LID). LID relies on a sequence of pre‐ and postsynaptic neuronal events, leading to abnormal corticostriatal neurotransmission and maladaptive changes in striatal projection neurons. In recent years, additional non‐neuronal mechanisms have been proposed to contribute to LID. Among these mechanisms, considerable attention has been focused onl ‐DOPA‐induced inflammatory responses. Microglia and astrocytes are the main actors in neuroinflammatory responses, and their double role at the interface between immune and neurophysiological responses is starting to be elucidated. Both microglia and astrocytes express a multitude of neurotransmitter receptors and via the release of several soluble molecules modulate synaptic function in neuronal networks. Here we review preclinical and clinical evidence of glial overactivation byl ‐DOPA, supporting a role of microglia and astrocytes in the development of LID. We propose that in PD, chronically and abnormally activated microglia and astrocytes lead to an aberrant neuron‐glia communication, which affect synaptic activity and neuroplasticity contributing to the development of LID. Abstract : l ‐DOPA‐induced dyskinesia (LID) is associated with striatal inflammatory responses, with chronically activated microglia and astrocytes, and overproduction of cytokines and NO. LID is modulated by agents increasing or decreasing neuroinflammation. Microglia and astrocytes‐released cytokines modulate synaptic function. Excessive release of inflammatory cytokines in the striatum may lead to an aberrant neuron‐glia cross‐talk by affecting synaptic activity, thereby contributing to LID development.