Synaptic plasticity and levodopa-induced dyskinesia: electrophysiological and structural abnormalities

Paolo Calabresi, Barbara Picconi, Elvira De Leonibus

Risultato della ricerca: Contributo in rivistaArticolo in rivista

15 Citazioni (Scopus)

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of dopaminergic neurons located in the midbrain. The gold-standard therapy for PD is the restoration of dopamine (DA) levels through the chronic administration of the DA precursor levodopa (L-DOPA). Although levodopa therapy is the main therapeutic approach for PD, its use is limited by the development of very disabling dyskinetic movements, mainly due to the fluctuation of DA cerebral content. Experimental animal models of PD identified in DA D1/ERK-signaling pathway aberrant activation, occurring in striatal projection neurons, coupled with structural spines abnormalities, the molecular and neuronal basis of L-DOPA-induced dyskinesia (LIDs) occurrence. Different electrophysiological approaches allowed the identification of the alteration of homeostatic structural and synaptic changes, the neuronal bases of LIDs either in vivo in parkinsonian patients or in vitro in experimental animals. Here, we report the most recent studies showing electrophysiological and morphological evidence of aberrant synaptic plasticity in parkinsonian patients during LIDs in different basal ganglia nuclei and also in cortical transmission, accounting for the complexity of the synaptic changes during dyskinesias. All together, these studies suggest that LIDs are associated with a loss of homeostatic synaptic mechanisms.
Lingua originaleEnglish
pagine (da-a)1263-1271
Numero di pagine9
RivistaJournal of Neural Transmission
Volume125
DOI
Stato di pubblicazionePubblicato - 2018

Keywords

  • Depotentiation
  • LIDs
  • Parkinson’s disease
  • Spine plasticity
  • Synaptic plasticity
  • Neuronal Plasticity
  • Antiparkinson Agents
  • Corpus Striatum
  • Dyskinesia, Drug-Induced
  • Humans
  • Levodopa
  • Animals

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