l-DOPA-induced dyskinesia and neuroinflammation: do microglia and astrocytes play a role?

Author(s)

Carta, Anna R. ; Mulas, Giovanna ; Bortolanza, Mariza ; Duarte, Terence ; Pillai, Elisabetta ; Fisone, Gilberto ; Vozari, Rita Raisman ; Del-Bel, Elaine

• Document type: Journal article
• Source: European Journal of Neuroscience; v. 45, n. 1, SI, p. 73-91, JAN 2017.
• Web of Science Citations: 10

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. (AU)

• FAPESP's process: 12/17626-7 - Cellular and molecular mechanisms involved in the role of atypical neurotransmitters in neuropsychiatric disorders
• Grantee: Francisco Silveira Guimaraes
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/25029-4 - Contribution of the neuroinflamation to L-DOPA induced dyskinesia
• Grantee: Elaine Aparecida Del Bel Belluz Guimarães
• Support Opportunities: Research Projects - Thematic Grants