title: Neuroprotective effect of rotigotine against complex I inhibitors, MPP⁺ and rotenone, in primary mesencephalic cell culture.
abstract: BACKGROUND
  Dopamine agonists are suggested to be more efficacious in treating Parkinson's disease (PD) as they have neuroprotective properties in addition to their receptor-related actions.
  
  
  OBJECTIVE
  The present study was designed to investigate the neuroprotective effects of rotigotine, a D3/D2/D1 dopamine receptor agonist, against the two powerful complex I inhibitors, 1-methyl-4-phenylpyridinium (MPP+) and rotenone, in primary mesencephalic cell culture relevant to PD.
  
  
  METHODS
  Primary mesencephalic cell cultures were prepared from embryonic mouse mesencephala at gestation day 14. Three sets of cultures were treated with rotigotine alone, rotigotine and MPP⁺, and rotigotine and rotenone to investigate the effect of rotigotine on the survival of dopaminergic neurons against age-, MPP⁺- and rotenone-induced cell death. At the end of each treatment, cultures were fixed and stained immunohistochemically against tyrosine hydroxylase (TH). The effect of rotigotine against rotenone-induced reactive oxygen species (ROS) production was measured using CH-H2DCFDA fluorescence dye.
  
  
  RESULTS
  Rotigotine alone did not influence the survival of tyrosine hydroxylase immunoreactive (THir) neurons except at 10 µM, it significantly decreased the number of THir neurons by 40% compared to untreated controls. Treatment of cultures with 0.01 µM rotigotine rescued 10% of THir neurons against MPP⁺-induced cell death. Rotigotine was also found to significantly rescue 20% of THir neurons at 0.01 µM of rotenone-treated cultures. Using of CH-H2DCFDA fluorescence dye, it was found that rotigotine significantly attenuated ROS production compared to rotenone-treated cultures.
  
  
  CONCLUSIONS
  Rotigotine provides minor protection against MPP⁺ and rescues a significant number of THir neurons against rotenone in primary mesencephalic cell cultures relevant to PD.
authors.affiliation: Dr. Khaled Radad, PhD, Department of Pathology, Faculty of Veterinary Medicine, Assiut University, Assiut 71526, Egypt, tel.: +2-882-333938, fax: +2-882-366503, e-mail: khaledradad@hotmail.com.
authors.forename: Khaled
authors.initials: K
authors.lastname: Radad
authors.forename: Dieter
authors.initials: D
authors.lastname: Scheller
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Rausch
authors.forename: Heinz
authors.initials: H
authors.lastname: Reichmann
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Gille
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D002478:Cells, Cultured; D007150:Immunohistochemistry; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000633:toxicity; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D014475:Uncoupling Agents / Q000633:toxicity
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D014475:Uncoupling Agents; D012402:Rotenone; C047508:rotigotine; D015655:1-Methyl-4-phenylpyridinium