What's wrong with the striatal cholinergic interneurons in Parkinson's disease? Focus on intrinsic excitability.
Eur J Neurosci
; 53(7): 2100-2116, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-32302030
Parkinson's disease (PD) is characterized by a degeneration of nigrostriatal dopaminergic neurons that results in a hypercholinergic state in the striatum. This hypercholinergic state contributes to the clinical signs of PD. However, the mechanisms that underlie this state remain unknown. Cholinergic interneurons (ChIs) are the main source of acetylcholine in the striatum. Many studies have highlighted the importance of their normal physiological activity to guarantee a normal motor control and goal-directed behaviour. Moreover, recent studies with optogenetic and chemogenetic approaches have shown that reducing ChIs activity ameliorates parkinsonian symptoms and modifies L-dopa induced dyskinesia in PD animal models. Here, we review the described alterations in ChIs physiology that may contribute to a hypercholinergic state in PD. The best-established finding is an increase of ChIs intrinsic membrane excitability after dopaminergic denervation of striatum. Understanding the molecular basis of ChIs dysfunction in PD could help to develop new therapeutic tools to restore their normal activity and decrease parkinsonian symptoms, improving life quality of PD patients.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Eur J Neurosci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Argentina
País de publicação:
França