title: Alterations in the expression of nNOS in the substantia nigra and subthalamic nucleus of 6-OHDA-lesioned rats: the effects of chronic treatment with l-DOPA and the nitric oxide donor, molsidomine.
abstract: Recently, it has been strongly suggested that reciprocal interactions between nitrergic and dopaminergic systems play a crucial role in the control of the nigrostriatal pathway. Degeneration of dopaminergic neurons in the substantia nigra (SN) in Parkinson's disease leads to disturbances in the nitrergic transmission in the basal ganglia. In the present study, we aimed to compare regional distribution of nNOS immunoreactivity and NADPH-diaphorase activity in the SN and subthalamic nucleus (STN) of unilaterally 6-OHDA-lesioned rats treated chronically with l-DOPA (25mg/kg) and the nitric oxide donor, molsidomine (2 or 4mg/kg). Our results showed that degeneration of dopaminergic neurons in the ipsilateral SN resulted in a 25% decrease in the number of nNOS-immunoreactive neurons in that structure and in nNOS protein level determined by Western blot. We also found that nNOS was present in about 70% of all SN neurons. NADPH-d histochemistry did not reveal nNOS activity in the SN of any studied groups. Furthermore, the stereological analysis of the SN volume showed that chronic administration of l-DOPA evoked a hypertrophy of the ipsilateral SN when compared to the contralateral side. Such difference between sides was abolished in the group receiving l-DOPA in combination with molsidomine. Degeneration of the nigrostriatal pathway had no influence on the number of nNOS-ir neurons in the STN. NADPH-histochemistry revealed nNOS activity only in a part of neurons of that structure. Our results make an essential contribution to the research on the role of nitric oxide in the regulation of basal ganglia function.
authors.affiliation: Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St., PL 31-343 Kraków, Poland. Electronic address: czarnec@if-pan.krakow.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Czarnecka
authors.forename: Tomasz
authors.initials: T
authors.lastname: Lenda
authors.forename: Helena
authors.initials: H
authors.lastname: Domin
authors.forename: Jolanta
authors.initials: J
authors.lastname: Konieczny
authors.forename: Maria
authors.initials: M
authors.lastname: Smiałowska
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Lorenc-Koci
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D015153:Blotting, Western; D007150:Immunohistochemistry; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008981:Molsidomine / Q000494:pharmacology; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000201:enzymology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis*; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology*; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000201:enzymology*
chemical_list: D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D020030:Nitric Oxide Donors; D007980:Levodopa; D016627:Oxidopamine; D008981:Molsidomine; D052248:Nitric Oxide Synthase Type I; D009252:NADPH Dehydrogenase
keywords: 6-OHDA; 6-hydroxydopamine; CV; Hypertrophy; MFB; NADPH-d; NO; Nitric oxide; PD; Parkinson's disease; SNc; SNr; STN; Substantia nigra; Subthalamic nucleus; TH; cresyl violet; l-DOPA; medial forebrain bundle; mol; molsidomine; nNOS; neuronal nitric oxide synthase; nicotinamide dinucleotide phosphate diaphorase; nitric oxide; substantia nigra pars compacta; substantia nigra pars reticulata; subthalamic nucleus; tyrosine hyroxylase