Ropinirole Cotreatment Prevents Perivascular Glial Recruitment in a Rat Model of L-DOPA-Induced Dyskinesia.
Ropinirole Cotreatment Prevents Perivascular Glial Recruitment in a Rat Model of L-DOPA-Induced Dyskinesia.
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DOI：
10.3390/cells12141859
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发表时间：
2023-07-14
期刊：
影响因子：
6
通讯作者：
Cenci MA
中科院分区：
文献类型：
--
作者：
Elabi OF;Espa E;Skovgård K;Fanni S;Cenci MA
帕金森病的多巴胺替代疗法是使用左旋多巴或多巴胺D2/3激动剂，如罗匹尼罗。在这里，我们比较了左旋多巴和罗匹尼罗单独或联合使用对纹状体中胶质和微血管反应性模式的影响。对单侧6-羟多巴胺病变的大鼠进行治疗性剂量的左旋多巴（6 mg/kg）、等效左旋多巴-罗匹尼罗联合（左旋多巴3 mg/kg +罗匹尼罗0.5 mg/kg）或单独罗匹尼罗治疗。免疫组织化学检测小胶质细胞（离子钙结合适配器分子1，IBA-1）和星形胶质细胞（胶质纤维酸性蛋白，GFAP）的反应性，血管密度（大鼠内皮细胞抗原1，RECA-1）和白蛋白外渗出。左旋多巴单药和左旋多巴-罗匹尼罗联合治疗可引起中重度运动障碍，而单独使用罗匹尼罗对运动障碍的影响可以忽略。尽管运动障碍的严重程度相似，但在左旋多巴与左旋多巴-罗匹尼罗治疗的动物之间，血管周围小胶质细胞和星形胶质细胞的反应性存在显著差异。前者表现出血管周围IBA-1细胞（部分cd68阳性）和IBA-1 - reca -1接触点的显著上调，微血管密度增加，血管周围GFAP表达增强。在左旋多巴-罗匹尼罗或单独使用罗匹尼罗治疗的动物中，这些标记物均未显着上调。综上所述，虽然罗匹尼罗联合治疗不能预防左旋多巴诱导的运动障碍，但它可以防止与该疾病相关的不适应胶质血管变化，对纹状体组织稳态有潜在的长期益处。
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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影响因子：
9.3
作者：
Elabi OF;Cunha JPMCM;Gaceb A;Fex M;Paul G
通讯作者：
Paul G
影响因子：
8.6
作者：
Boi, Laura;Pisanu, Augusta;Carta, Anna R.
通讯作者：
Carta, Anna R.
影响因子：
3.3
作者：
Espinosa-Cardenas, Raquel;Arce-Sillas, Asiel;Adalid-Peralta, Laura
通讯作者：
Adalid-Peralta, Laura
影响因子：
4.7
作者：
Grigoriou, Sotirios;Espa, Elena;Cenci, M. Angela
通讯作者：
Cenci, M. Angela
影响因子：
3.7
作者：
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通讯作者：
Chen, Lei