Nigrostriatal system plasticity in Parkinson's disease : Effect of dopaminergic denervation and treatment. Discussion
Identifieur interne : 003B67 ( Main/Curation ); précédent : 003B66; suivant : 003B68Nigrostriatal system plasticity in Parkinson's disease : Effect of dopaminergic denervation and treatment. Discussion
Auteurs : E. C. Hirsch [France] ; BENABID ; OLANOW ; SEALFON ; HALLETT ; LANGSTON ; CALABRESISource :
- Annals of neurology [ 0364-5134 ] ; 2000.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
- Antiparkinson agent, Corpus Striatum (drug effects), Corpus Striatum (physiopathology), Dopamine (physiology), Dopamine Agents (adverse effects), Dyskinesia, Dyskinesia, Drug-Induced (physiopathology), Human, Humans, Levodopa, Levodopa (adverse effects), Nerve Degeneration (chemically induced), Nerve Degeneration (physiopathology), Neuronal Plasticity (drug effects), Nigrostriatal pathway, Parkinson Disease (drug therapy), Parkinson Disease (physiopathology), Parkinson disease, Pathophysiology, Review, Substantia Nigra (drug effects), Substantia Nigra (physiopathology), Synaptic plasticity.
- MESH :
- chemical , adverse effects : Dopamine Agents, Levodopa.
- chemical , physiology : Dopamine.
- chemically induced : Nerve Degeneration.
- drug effects : Corpus Striatum, Neuronal Plasticity, Substantia Nigra.
- drug therapy : Parkinson Disease.
- physiopathology : Corpus Striatum, Dyskinesia, Drug-Induced, Nerve Degeneration, Parkinson Disease, Substantia Nigra.
- Humans.
Abstract
Clinical studies suggest that the appearance of levodopa-induced dyskinesias may be partly related to changes in the dopaminergic system. This article reviews data on biochemical and morphological changes induced by treatment, the lesion, or both, in dopaminergic neurons themselves, postsynaptic striatal tissue, and afferent fibers to dopaminergic neurons in the substantia nigra. Recent studies on dopaminergic neurons suggest that levodopa therapy can induce sprouting of surviving dopaminergic neurons at their terminals in the striatum. At the postsynaptic level, treatment may trigger induction of D3 dopamine receptors and internalization of D1 receptors. Furthermore, dopaminergic denervation has been shown to be involved in plastic changes in the striatum associated with hyperactivity of glutamatergic fibers making synapses with the head of the spines of γ-aminobutyric acid-ergic neurons. At the level of the dendrites of dopaminergic neurons, plasticity of excitatory cholinergic afferent fibers targeting dopaminergic neurons and an involution of noncholinergic afferent fibers have been observed. Taken together, these data suggest that dopaminergic denervation and treatment induce profound plastic changes in the nigrostriatal system. Whether such changes participate in side-effects of treatment and, in particular, the appearance of dyskinesias remains to be determined.
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<front><div type="abstract" xml:lang="en">Clinical studies suggest that the appearance of levodopa-induced dyskinesias may be partly related to changes in the dopaminergic system. This article reviews data on biochemical and morphological changes induced by treatment, the lesion, or both, in dopaminergic neurons themselves, postsynaptic striatal tissue, and afferent fibers to dopaminergic neurons in the substantia nigra. Recent studies on dopaminergic neurons suggest that levodopa therapy can induce sprouting of surviving dopaminergic neurons at their terminals in the striatum. At the postsynaptic level, treatment may trigger induction of D3 dopamine receptors and internalization of D1 receptors. Furthermore, dopaminergic denervation has been shown to be involved in plastic changes in the striatum associated with hyperactivity of glutamatergic fibers making synapses with the head of the spines of gamma-aminobutyric acidergic neurons. At the level of the dendrites of dopaminergic neurons, plasticity of excitatory cholinergic afferent fibers targeting dopaminergic neurons and an involution of noncholinergic afferent fibers have been observed. Taken together, these data suggest that dopaminergic denervation and treatment induce profound plastic changes in the nigrostriatal system. Whether such changes participate in side-effects of treatment and, in particular, the appearance of dyskinesias remains to be determined.</div>
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