title: Neuroprotective Effect of Progesterone in MPTP-Treated Male Mice.
abstract: Numerous studies have reported on the neuroprotective activity of estradiol, whereas the effect of the other ovarian steroid, progesterone, is much less documented.
  
  
  
  This study sought to investigate neuroprotection with a low dose of progesterone (1 µg) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated male mice to model Parkinson's disease and compare it to the effect of this steroid in intact mice (experiment 1). We also investigated if high doses of progesterone could protect dopaminergic neurons already exposed to MPTP (experiment 2). We measured progesterone effects on various dopaminergic markers [dopamine and its metabolites, dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2)] and on neuroactive steroids in both plasma and the brain.
  
  
  
  For experiment 1, our results showed that progesterone completely prevented the effect of MPTP toxicity on dopamine concentrations, on the increase in the 3-methoxytyramine/dopamine ratio, as well as on VMAT2-specific binding in the striatum and the substantia nigra. Progesterone decreased MPTP effects on 3,4-dihydroxyphenylacetic acid concentrations and DAT-specific binding in the lateral part of the anterior striatum and in the middle striatum (medial and lateral parts). Progesterone treatment of intact mice had no effect on the markers investigated. For experiment 2, measures of dopaminergic markers in the striatum showed that 8 mg/kg of progesterone was the most effective dose to reduce MPTP effects, and more limited effects were observed with 16 mg/kg. We found that progesterone treatment increases the levels of brain progesterone itself as well as of its metabolites.
  
  
  
  Our result showed that progesterone has neuroprotective effects on dopaminergic neurons in MPTP-treated male mice.
authors.affiliation: Neuroscience Research Unit, Centre Hospitalier Universitaire de Qux00E9;bec, Centre Hospitalier de l'Universitx00E9; Laval, Quebec City, Que., Canada.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Bourque
authors.forename: Marc
authors.initials: M
authors.lastname: Morissette
authors.forename: Sara
authors.initials: S
authors.lastname: Al Sweidi
authors.forename: Donatella
authors.initials: D
authors.lastname: Caruso
authors.forename: Roberto C
authors.initials: RC
authors.lastname: Melcangi
authors.forename: Thérèse
authors.initials: T
authors.lastname: Di Paolo
mesh_terms: D015113:Androstane-3,17-diol / Q000031:analogs & derivatives / Q000097:blood; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003042:Cocaine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D013196:Dihydrotestosterone / Q000097:blood; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D020267:MPTP Poisoning / Q000097:blood / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011374:Progesterone / Q000097:blood / Q000627:therapeutic use*; D013739:Testosterone / Q000097:blood; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
chemical_list: D002250:Carbon Radioisotopes; D050483:Dopamine Plasma Membrane Transport Proteins; D018696:Neuroprotective Agents; C493453:Slc18a2 protein, mouse; D050493:Vesicular Monoamine Transport Proteins; D013196:Dihydrotestosterone; C079213:RTI 121; D015113:Androstane-3,17-diol; D013739:Testosterone; D011374:Progesterone; C042903:androstane-3,7-diol disulfate; D003042:Cocaine; D004298:Dopamine