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Synaptic dysfunction in Parkinson's disease.
Biochem Soc Trans. 2010 Apr; 38(2):493-7.BS

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, but most 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.

Authors+Show Affiliations

Laboratorio di Neurofisiologia, Fondazione Santa Lucia, I.R.C.C.S., 00143 Rome, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

20298209

Citation

Bagetta, Vincenza, et al. "Synaptic Dysfunction in Parkinson's Disease." Biochemical Society Transactions, vol. 38, no. 2, 2010, pp. 493-7.
Bagetta V, Ghiglieri V, Sgobio C, et al. Synaptic dysfunction in Parkinson's disease. Biochem Soc Trans. 2010;38(2):493-7.
Bagetta, V., Ghiglieri, V., Sgobio, C., Calabresi, P., & Picconi, B. (2010). Synaptic dysfunction in Parkinson's disease. Biochemical Society Transactions, 38(2), 493-7. https://doi.org/10.1042/BST0380493
Bagetta V, et al. Synaptic Dysfunction in Parkinson's Disease. Biochem Soc Trans. 2010;38(2):493-7. PubMed PMID: 20298209.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synaptic dysfunction in Parkinson's disease. AU - Bagetta,Vincenza, AU - Ghiglieri,Veronica, AU - Sgobio,Carmelo, AU - Calabresi,Paolo, AU - Picconi,Barbara, PY - 2010/3/20/entrez PY - 2010/3/20/pubmed PY - 2010/6/12/medline SP - 493 EP - 7 JF - Biochemical Society transactions JO - Biochem Soc Trans VL - 38 IS - 2 N2 - 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, but most 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. SN - 1470-8752 UR - https://www.unboundmedicine.com/medline/citation/20298209/Synaptic_dysfunction_in_Parkinson's_disease_ L2 - https://portlandpress.com/biochemsoctrans/article-lookup/doi/10.1042/BST0380493 DB - PRIME DP - Unbound Medicine ER -