Are cyclooxygenase-2 and nitric oxide involved in the dyskinesia of Parkinson%26apos;s disease induced by L-DOPA?

作者：Bortolanza Mariza; Padovan Neto Fernando E; Cavalcanti Kiwiatkoski Roberta; dos Santos Pereira Mauricio; Mitkovski Miso; Raisman Vozari Rita; Del Bel Elaine

来源：Philosophical Transactions of the Royal Society B-Biological Sciences, 2015, 370(1672): UNSP 20140190.

DOI：10.1098/rstb.2014.0190

• COX2
• prostaglandin H-synthase
• neuroinflammation
• striatum interneurons
• volume transmission
• extrasynaptic signalling

Inflammatory mechanisms are proposed to play a role in L-DOPA-induced dyskinesia. Cyclooxygenase-2 (COX2) contributes to inflammation pathways in the periphery and is constitutively expressed in the central nervous system. Considering that inhibition of nitric oxide (NO) formation attenuates L-DOPA-induced dyskinesia, this study aimed at investigating if a NO synthase (NOS) inhibitor would change COX2 brain expression in animals with L-DOPA-induced dyskinesia. To this aim, male Wistar rats received unilateral 6-hydroxydopamine microinjection into the medial forebrain bundle were treated daily with L-DOPA (21 days) combined with 7-nitroindazole or vehicle. All hemi-Parkinsonian rats receiving L-DOPA showed dyskinesia. They also presented increased neuronal COX2 immunoreactivity in the dopamine-depleted dorsal striatum that was directly correlated with dyskinesia severity. Striatal COX2 co-localized with choline-acetyltransferase, calbindin and DARPP-32 (dopamine-cAMP-regulated phosphoprotein-32), neuronal markers of GABAergic neurons. NOS inhibition prevented L-DOPA-induced dyskinesia and COX2 increased expression in the dorsal striatum. These results suggest that increased COX2 expression after L-DOPA long-term treatment in Parkinsonian-like rats could contribute to the development of dyskinesia.

• 出版日期2015-7-5