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

Elabi, Osama F LU ; Espa, Elena LU orcid ; Skovgård, Katrine LU ; Fanni, Silvia LU and Cenci, Maria Angela LU orcid (2023) In Cells 12(14).
Abstract

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... (More)

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.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Rats, Animals, Levodopa, Antiparkinson Agents/adverse effects, Microglia/metabolism, Dopamine, Dyskinesia, Drug-Induced/drug therapy, Dopamine Agonists/pharmacology
in
Cells
volume
12
issue
14
article number
1859
publisher
MDPI AG
external identifiers
  • scopus:85165870635
  • pmid:37508522
ISSN
2073-4409
DOI
10.3390/cells12141859
language
English
LU publication?
yes
id
ab2cb359-644e-4ffe-a356-625b8cc07fd6
date added to LUP
2023-09-19 09:29:35
date last changed
2024-11-30 01:11:09
@article{ab2cb359-644e-4ffe-a356-625b8cc07fd6,
  abstract     = {{<p>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.</p>}},
  author       = {{Elabi, Osama F and Espa, Elena and Skovgård, Katrine and Fanni, Silvia and Cenci, Maria Angela}},
  issn         = {{2073-4409}},
  keywords     = {{Rats; Animals; Levodopa; Antiparkinson Agents/adverse effects; Microglia/metabolism; Dopamine; Dyskinesia, Drug-Induced/drug therapy; Dopamine Agonists/pharmacology}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{14}},
  publisher    = {{MDPI AG}},
  series       = {{Cells}},
  title        = {{Ropinirole Cotreatment Prevents Perivascular Glial Recruitment in a Rat Model of L-DOPA-Induced Dyskinesia}},
  url          = {{http://dx.doi.org/10.3390/cells12141859}},
  doi          = {{10.3390/cells12141859}},
  volume       = {{12}},
  year         = {{2023}},
}