title: Are cyclooxygenase-2 and nitric oxide involved in the dyskinesia of Parkinson's disease induced by L-DOPA?
abstract: 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.
authors.affiliation: School of Odontology of Ribeirão Preto, Department of Morphology, University of São Paulo (USP), Physiology and Basic Pathology, Av. Café S/N, 14040-904, Ribeirão Preto, São Paulo, Brazil Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, São Paulo, Brazil.
authors.forename: Mariza
authors.initials: M
authors.lastname: Bortolanza
authors.affiliation: Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, São Paulo, Brazil Department of Behavioural Neurosciences, Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, São Paulo, Brazil.
authors.forename: Fernando E
authors.initials: FE
authors.lastname: Padovan-Neto
authors.affiliation: Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, São Paulo, Brazil Medical School, Department of Physiology, University of Sao Paulo, São Paulo, Brazil.
authors.forename: Roberta
authors.initials: R
authors.lastname: Cavalcanti-Kiwiatkoski
authors.affiliation: Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, São Paulo, Brazil Medical School, Department of Physiology, University of Sao Paulo, São Paulo, Brazil.
authors.forename: Maurício
authors.initials: M
authors.lastname: Dos Santos-Pereira
authors.affiliation: Light Microscopy Facility, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075 Göttingen, Germany.
authors.forename: Miso
authors.initials: M
authors.lastname: Mitkovski
authors.affiliation: Institut de Cerveau et de la Moelle Epinière, Sorbonne Université UPMC UM75 INSERM U1127, CNRS UMR 7225, Paris, France.
authors.forename: Rita
authors.initials: R
authors.lastname: Raisman-Vozari
authors.affiliation: School of Odontology of Ribeirão Preto, Department of Morphology, University of São Paulo (USP), Physiology and Basic Pathology, Av. Café S/N, 14040-904, Ribeirão Preto, São Paulo, Brazil Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, São Paulo, Brazil Department of Behavioural Neurosciences, Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, São Paulo, Brazil Medical School, Department of Physiology, University of Sao Paulo, São Paulo, Brazil eadelbel@forp.usp.br.
authors.forename: Elaine
authors.initials: E
authors.lastname: Del-Bel
mesh_terms: D000818:Animals; D064026:Calbindins / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism*; D007150:Immunohistochemistry; D007980:Levodopa / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D016627:Oxidopamine / Q000008:administration & dosage / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D064026:Calbindins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497930:Ppp1r1b protein, rat; D009569:Nitric Oxide; D007980:Levodopa; D016627:Oxidopamine; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2
keywords: COX2; extrasynaptic signalling; neuroinflammation; prostaglandin H-synthase; striatum interneurons; volume transmission