Synaptic dysfunction in Parkinson's disease

Vincenza Bagetta, Veronica Ghiglieri, Carmelo Sgobio, Paolo Calabresi, Barbara Picconi

Research output: Contribution to journalArticle

Abstract

In neuronal circuits, memory storage depends on activity-dependent modifications in synaptic efficacy, such as LTD (long-term depression) and LTP (long-term potentiation), the two main forms of synaptic plasticity in the brain. In the nucleus striatum, LTD and LTP represent key cellular substrates for adaptive motor control and procedural memory. It has been suggested that their impairment could account for the onset and progression of motor symptoms of PD (Parkinson's disease), a neurodegenerative disorder characterized by the massive degeneration of dopaminergic neurons projecting to the striatum. In fact, a peculiar aspect of striatal plasticity is the modulation exerted by DA (dopamine) on LTP and LTD. Our understanding of these maladaptive forms of plasticity has mostly come from the electrophysiological, molecular and behavioural analyses of experimental animal models of PD. In PD, a host of cellular and synaptic changes occur in the striatum in response to the massive loss of DA innervation. Chronic L-dopa therapy restores physiological synaptic plasticity and behaviour in treated PD animals, butmost of them, similarly to patients, exhibit a reduction in the efficacy of the drug and disabling AIMs (abnormal involuntary movements) defined, as a whole, as L-dopa-induced dyskinesia. In those animals experiencing AIMs, synaptic plasticity is altered and is paralleled by modifications in the postsynaptic compartment. In particular, dysfunctions in trafficking and subunit composition of NMDARs [NMDA (N-methyl-D-aspartate) receptors] on striatal efferent neurons result from chronic non-physiological dopaminergic stimulation and contribute to the pathogenesis of dyskinesias. According to these pathophysiological concepts, therapeutic strategies targeting signalling proteins coupled to NMDARs within striatal spiny neurons could represent new pharmaceutical interventions for PD and L-dopa-induced dyskinesia.

Original languageEnglish
Pages (from-to)493-497
Number of pages5
JournalBiochemical Society Transactions
Volume38
Issue number2
DOIs
Publication statusPublished - Apr 2010

Fingerprint

Dyskinesias
Plasticity
Parkinson Disease
Levodopa
Corpus Striatum
Neurons
Neuronal Plasticity
Long-Term Potentiation
Animals
N-Methylaspartate
N-Methyl-D-Aspartate Receptors
Dopamine
Depression
Data storage equipment
Efferent Neurons
Pharmaceutical Preparations
Brain
Dopaminergic Neurons
Protein Transport
Modulation

Keywords

  • Dopamine
  • Dyskinesia
  • N-methyl-D-aspartate receptor (NMDA receptor)
  • Parkinson's disease
  • Striatum
  • Synaptic plasticity

ASJC Scopus subject areas

  • Biochemistry

Cite this

Synaptic dysfunction in Parkinson's disease. / Bagetta, Vincenza; Ghiglieri, Veronica; Sgobio, Carmelo; Calabresi, Paolo; Picconi, Barbara.

In: Biochemical Society Transactions, Vol. 38, No. 2, 04.2010, p. 493-497.

Research output: Contribution to journalArticle

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