title: l-DOPA-induced dyskinesia and neuroinflammation: do microglia and astrocytes play a role?
abstract: In Parkinson's disease (PD), l-DOPA therapy leads to the emergence of motor complications including l-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 on l-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 by l-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.
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, S.P. N. 8, 09042, Monserrato, Cagliari, Italy.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Carta
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, S.P. N. 8, 09042, Monserrato, Cagliari, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mulas
authors.affiliation: School of Odontology of Ribeirão Preto, Department of Morphology, Physiology and Basic Pathology, University of São Paulo (USP), Av. Café S/N, 14040-904, Ribeirão Preto, SP, Brazil.|USP, Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), São Paulo, Brazil.
authors.forename: Mariza
authors.initials: M
authors.lastname: Bortolanza
authors.affiliation: School of Odontology of Ribeirão Preto, Department of Morphology, Physiology and Basic Pathology, University of São Paulo (USP), Av. Café S/N, 14040-904, Ribeirão Preto, SP, Brazil.|USP, Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), São Paulo, Brazil.
authors.forename: Terence
authors.initials: T
authors.lastname: Duarte
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, S.P. N. 8, 09042, Monserrato, Cagliari, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pillai
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177, Stockholm, Sweden.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Fisone
authors.affiliation: INSERM U 1127, CNRS UMR 7225, UPMC Univ Paris 06, UMR S 1127, Institut Du Cerveau et de La Moelle Epiniére, ICM, Paris, France.
authors.forename: Rita Raisman
authors.initials: RR
authors.lastname: Vozari
authors.affiliation: School of Odontology of Ribeirão Preto, Department of Morphology, Physiology and Basic Pathology, University of São Paulo (USP), Av. Café S/N, 14040-904, Ribeirão Preto, SP, Brazil.
authors.forename: Elaine
authors.initials: E
authors.lastname: Del-Bel
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects*; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D006801:Humans; D017628:Microglia / Q000187:drug effects*; D010300:Parkinson Disease / Q000188:drug therapy*
chemical_list: D000978:Antiparkinson Agents
keywords: Parkinson's disease; cytokine; inducible nitric oxide synthase; nitric oxide; tumor necrosis factor-α