OBJECTIVE: Spreading depolarization (SD) is a transient self-propagating wave of neuronal and glial depolarization coupled with large membrane ionic changes and a subsequent depression of neuronal activity. Spreading depolarization in the cortex is implicated in migraine, stroke, and epilepsy. Conversely, spreading depolarization in the striatum, a brain structure deeply involved in motor control and in Parkinson's disease (PD) pathophysiology, has been poorly investigated. METHODS: We characterized the participation of glutamatergic and dopaminergic transmission in the induction of striatal spreading depolarization by using a novel approach combining optical imaging, measurements of endogenous DA levels, and pharmacological and molecular analyses. RESULTS: We found that striatal spreading depolarization requires the concomitant activation of D1-like DA and N-methyl-d-aspartate receptors, and it is reduced in experimental PD. Chronic l-dopa treatment, inducing dyskinesia in the parkinsonian condition, increases the occurrence and speed of propagation of striatal spreading depolarization, which has a direct impact on one of the signaling pathways downstream from the activation of D1 receptors. CONCLUSION: Striatal spreading depolarization might contribute to abnormal basal ganglia activity in the dyskinetic condition and represents a possible therapeutic target.

Striatal spreading depolarization: Possible implication in levodopa-induced dyskinetic-like behavior / de Iure, Antonio; Napolitano, Francesco; Beck, Goichi; Quiroga Varela, Ana; Durante, Valentina; Sciaccaluga, Miriam; Mazzocchetti, Petra; Megaro, Alfredo; Tantucci, Michela; Cardinale, Antonella; Punzo, Daniela; Mancini, Andrea; Costa, Cinzia; Ghiglieri, Veronica; Tozzi, Alessandro; Picconi, Barbara; Papa, Stella M.; Usiello, Alessandro; Calabresi, Paolo. - In: MOVEMENT DISORDERS. - ISSN 0885-3185. - (2019). [10.1002/mds.27632]

Striatal spreading depolarization: Possible implication in levodopa-induced dyskinetic-like behavior

Francesco Napolitano;
2019

Abstract

OBJECTIVE: Spreading depolarization (SD) is a transient self-propagating wave of neuronal and glial depolarization coupled with large membrane ionic changes and a subsequent depression of neuronal activity. Spreading depolarization in the cortex is implicated in migraine, stroke, and epilepsy. Conversely, spreading depolarization in the striatum, a brain structure deeply involved in motor control and in Parkinson's disease (PD) pathophysiology, has been poorly investigated. METHODS: We characterized the participation of glutamatergic and dopaminergic transmission in the induction of striatal spreading depolarization by using a novel approach combining optical imaging, measurements of endogenous DA levels, and pharmacological and molecular analyses. RESULTS: We found that striatal spreading depolarization requires the concomitant activation of D1-like DA and N-methyl-d-aspartate receptors, and it is reduced in experimental PD. Chronic l-dopa treatment, inducing dyskinesia in the parkinsonian condition, increases the occurrence and speed of propagation of striatal spreading depolarization, which has a direct impact on one of the signaling pathways downstream from the activation of D1 receptors. CONCLUSION: Striatal spreading depolarization might contribute to abnormal basal ganglia activity in the dyskinetic condition and represents a possible therapeutic target.
2019
Striatal spreading depolarization: Possible implication in levodopa-induced dyskinetic-like behavior / de Iure, Antonio; Napolitano, Francesco; Beck, Goichi; Quiroga Varela, Ana; Durante, Valentina; Sciaccaluga, Miriam; Mazzocchetti, Petra; Megaro, Alfredo; Tantucci, Michela; Cardinale, Antonella; Punzo, Daniela; Mancini, Andrea; Costa, Cinzia; Ghiglieri, Veronica; Tozzi, Alessandro; Picconi, Barbara; Papa, Stella M.; Usiello, Alessandro; Calabresi, Paolo. - In: MOVEMENT DISORDERS. - ISSN 0885-3185. - (2019). [10.1002/mds.27632]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/738022
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