Abstract：
BACKGROUND AND PURPOSE:Rho kinase (ROCK) activation is involved in neuroinflammatory processes leading to progression of neurodegenerative diseases such as Parkinson's disease. Furthermore, ROCK plays a major role in angiogenesis. Neuroinflammation and angiogenesis are mechanisms involved in developing l-DOPA-induced dyskinesias (LID). However, it is not known whether ROCK plays a role in LID and whether ROCK inhibitors may be useful against LID. EXPERIMENTAL APPROACH:In rats, we performed short- and long-term dopaminergic lesions using 6-hydroxydopamine and developed a LID model. Effects of dopaminergic lesions and LID on the RhoA/ROCK levels were studied by western blot, real-time PCR analyses and ROCK activity assays in the substantia nigra and striatum. The effects of the ROCK inhibitor fasudil on LID were particularly investigated. KEY RESULTS:Short-term 6-hydroxydopamine lesions increased nigrostriatal RhoA/ROCK expression, apparently related to the active neuroinflammatory process. However, long-term dopaminergic denervation (completed and stabilized lesions) led to a decrease in RhoA/ROCK levels. Rats with LID showed a significant increase of RhoA and ROCK expression. The development of LID was reduced by the ROCK inhibitor fasudil (10 and 40 mg·kg-1 ), without interfering with the therapeutic effect of l-DOPA. Interestingly, treatment of 40 mg·kg-1 of fasudil also induced a significant reduction of dyskinesia in rats with previously established LID. CONCLUSION AND IMPLICATIONS:The present results suggest that ROCK is involved in the pathophysiology of LID and that ROCK inhibitors such as fasudil may be a novel target for preventing or treating LID. Furthermore, previous studies have revealed neuroprotective effects of ROCK inhibitors.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Lopez-Lopez A,Labandeira CM,Labandeira-Garcia JL,Muñoz Adoi
10.1111/bph.15275subject
Has Abstractpub_date
2020-12-01 00:00:00pages
5622-5641issue
24eissn
0007-1188issn
1476-5381journal_volume
177pub_type
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14645.x
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb09300.x
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journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1985.tb08825.x
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journal_title：British journal of pharmacology
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journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1989.tb12011.x
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb11281.x
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journal_title：British journal of pharmacology
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb14355.x
更新日期：1992-06-01 00:00:00
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doi：10.1038/sj.bjp.0703425
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pub_type： 杂志文章
doi：10.1111/bph.13044
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1971.tb09936.x
更新日期：1971-01-01 00:00:00
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journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1981.tb10428.x
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doi：10.1111/j.1476-5381.1977.tb07554.x
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更新日期：1997-10-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13447.x
更新日期：1993-01-01 00:00:00
