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 language | English |
|---|---|
| Pages (from-to) | 493-497 |
| Number of pages | 5 |
| Journal | Biochemical Society Transactions |
| Volume | 38 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Apr 2010 |
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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 journal › Article
}
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 - 2010/4
Y1 - 2010/4
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, 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.
AB - 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.
KW - Dopamine
KW - Dyskinesia
KW - N-methyl-D-aspartate receptor (NMDA receptor)
KW - Parkinson's disease
KW - Striatum
KW - Synaptic plasticity
UR - http://www.scopus.com/inward/record.url?scp=77953242721&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953242721&partnerID=8YFLogxK
U2 - 10.1042/BST0380493
DO - 10.1042/BST0380493
M3 - Article
C2 - 20298209
AN - SCOPUS:77953242721
VL - 38
SP - 493
EP - 497
JO - Biochemical Society Transactions
JF - Biochemical Society Transactions
SN - 0300-5127
IS - 2
ER -