Ropinirole Cotreatment Prevents Perivascular Glial Recruitment in a Rat Model of L-DOPA-Induced Dyskinesia

• Published in: Cells (Basel, Switzerland) Vol. 12; no. 14; p. 1859
• Main Authors: Elabi, Osama F, Espa, Elena, Skovgård, Katrine, Fanni, Silvia, Cenci, Maria Angela
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.07.2023; MDPI
• Subjects: 6-Hydroxydopamine; Animals; Antibodies; Antiparkinson Agents - adverse effects; Astrocytes; Basic Medicine; Causes of; Complications and side effects; Denervation; Dopa; Dopamine; dopamine agonist; Dopamine Agonists - pharmacology; Dopamine Agonists - therapeutic use; Dopamine D2 receptors; Dosage and administration; Drug dosages; Drug interactions; Drug therapy; Dyskinesia; Dyskinesia, Drug-Induced - drug therapy; Endothelial cells; Extravasation; Glial fibrillary acidic protein; Health aspects; Homeostasis; Immunohistochemistry; Laboratories; Levodopa; levodopa-induced dyskinesia; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Microglia; Microglia - metabolism; Microvasculature; Movement disorders; Neostriatum; Neurodegenerative diseases; Neuroglia; neuroinflammation; Neurosciences; Neurovetenskaper; Parkinson's disease; Patient outcomes; Pharmacology, Experimental; Rats; RecA protein; Ropinirole; Surgery; Sweden; United States > US; neuroinflammation; levodopa-induced dyskinesia; dopamine agonist
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells12141859

Dopamine replacement therapy for Parkinson's disease is achieved using L-DOPA or dopamine D2/3 agonists, such as ropinirole. Here, we compare the effects of L-DOPA and ropinirole, alone or in combination, on patterns of glial and microvascular reactivity in the striatum. Rats with unilateral 6-hydroxydopamine lesions were treated with therapeutic-like doses of L-DOPA (6 mg/kg), an equipotent L-DOPA-ropinirole combination (L-DOPA 3 mg/kg plus ropinirole 0.5 mg/kg), or ropinirole alone. Immunohistochemistry was used to examine the reactivity of microglia (ionized calcium-binding adapter molecule 1, IBA-1) and astroglia (glial fibrillary acidic protein, GFAP), as well as blood vessel density (rat endothelial cell antigen 1, RECA-1) and albumin extravasation. L-DOPA monotreatment and L-DOPA-ropinirole cotreatment induced moderate-severe dyskinesia, whereas ropinirole alone had negligible dyskinetic effects. Despite similar dyskinesia severity, striking differences in perivascular microglia and astroglial reactivity were found between animals treated with L-DOPA vs. L-DOPA-ropinirole. The former exhibited a marked upregulation of perivascular IBA-1 cells (in part CD68-positive) and IBA-1-RECA-1 contact points, along with an increased microvessel density and strong perivascular GFAP expression. None of these markers were significantly upregulated in animals treated with L-DOPA-ropinirole or ropinirole alone. In summary, although ropinirole cotreatment does not prevent L-DOPA-induced dyskinesia, it protects from maladaptive gliovascular changes otherwise associated with this disorder, with potential long-term benefits to striatal tissue homeostasis.