Artículo
Mechanisms of Antiparkinsonian Anticholinergic Therapy Revisited
Fecha de publicación:
07/2021
Editorial:
Pergamon-Elsevier Science Ltd
Revista:
Neuroscience
ISSN:
0306-4522
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Before the advent of L-DOPA, the gold standard symptomatic therapy for Parkinson's disease (PD), anticholinergic drugs (muscarinic receptor antagonists) were the preferred antiparkinsonian therapy, but their unwanted side effects associated with impaired extrastriatal cholinergic function limited their clinical utility. Since most patients treated with L-DOPA also develop unwanted side effects such as L-DOPA-induced dyskinesia (LID), better therapies are needed. Recent studies in animal models demonstrate that optogenetic and chemogenetic manipulation of striatal cholinergic interneurons (SCIN), the main source of striatal acetylcholine, modulate parkinsonism and LID, suggesting that restoring SCIN function might serve as a therapeutic option that avoids extrastriatal anticholinergics’ side effects. However, it is still unclear how the altered SCIN activity in PD and LID affects the striatal circuit, whereas the mechanisms of action of anticholinergic drugs are still not fully understood. Recent animal model studies showing that SCINs undergo profound changes in their tonic discharge pattern after chronic L-DOPA administration call for a reexamination of classical views of how SCINs contribute to PD symptoms and LID. Here, we review the recent advances on the circuit implications of aberrant striatal cholinergic signaling in PD and LID in an effort to provide a comprehensive framework to understand the effects of anticholinergic drugs and with the aim of shedding light into future perspectives of cholinergic circuit-based therapies.
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(IFIBIO HOUSSAY)
Articulos de INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Articulos de INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Citación
Paz, Rodrigo Manuel; Murer, Mario Gustavo; Mechanisms of Antiparkinsonian Anticholinergic Therapy Revisited; Pergamon-Elsevier Science Ltd; Neuroscience; 467; 7-2021; 201-217
Compartir
Altmétricas