Regulating astrocytic activity in the dorsal striatum mitigates L-dopa-induced dyskinesia in Parkinson’s disease
Abstract In Parkinson’s disease (PD), long-term 3,4-dihydroxy-L-phenylalanine (L-dopa) therapy leads to the development of motor complications, including L-dopa-induced dyskinesia (LID). Increased numbers of reactive astrocytes in the brains of patients with PD are a key feature of this disease. Ast...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-12104-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Abstract In Parkinson’s disease (PD), long-term 3,4-dihydroxy-L-phenylalanine (L-dopa) therapy leads to the development of motor complications, including L-dopa-induced dyskinesia (LID). Increased numbers of reactive astrocytes in the brains of patients with PD are a key feature of this disease. Astrocytes are involved in the development of LID; however, whether the regulation of astrocytic activity influences LID development remains unclear. Therefore, this study aimed to determine the effect of the direct modulation of glial fibrillary acidic protein (GFAP)-expressing glia on LID development during L-dopa therapy in PD using chemogenetic tools. Adeno-associated viruses (AAVs) were used to target designer receptors exclusively activated by designer drugs (DREADDs) in GFAP-expressing cells to modulate Gq- or Gi-mediated signaling and regulate astrocytic activity in the brain. AAVs were injected into the dorsal striatum, and 6-hydroxydopamine (6-OHDA) was injected into the substantia nigra of mice. Clozapine N-oxide was co-administered with L-dopa. Chemogenetic activation of astrocytes in the dopamine-depleted striatum affected the early development of LID in 6-OHDA-lesioned mice. Furthermore, astrocyte suppression through Gi-mediated DREADD reduced abnormal involuntary movement scores in mice. These results suggest that regulating astrocytic activity in the dorsal striatum could be a therapeutic option for LID in PD. |
|---|---|
| ISSN: | 2045-2322 |