title: Effects of progesterone administered after MPTP on dopaminergic neurons of male mice.
abstract: Progesterone neuroprotection of striatal dopamine (DA) in male mice lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was previously reported when administered before MPTP or an hour after. A dose of MPTP to induce a partial lesion was used to model early stages or prodromal Parkinson. We hypothesized that brain DA can be restored by progesterone administered early (24 h) or later (5 days) after MPTP. Male mice received 4 injections of MPTP (8 mg/kg) and progesterone (8 mg/kg) once daily for 5 days started 24 h or 5 days after MPTP. The lesion decreased striatal DA and its metabolites but not serotonin contents. MPTP mice treated with progesterone starting 24 h but not 5 days after MPTP had higher striatal DA and its metabolites content than vehicle-treated MPTP mice. Striatal DA transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) specific binding decreased in lesioned mice and were corrected with progesterone treatment starting 24 h but not 5 days after MPTP. Striatal glial fibrillary acidic protein (GFAP) levels, a marker of activated astrocytes, were elevated by the MPTP lesion and were corrected with progesterone treatment starting 24 h after MPTP. Striatal brain derived neurotrophic factor (BDNF) levels were decreased by the MPTP lesion and were prevented by progesterone treatments whereas no change of Akt, GSK3β, ERK1 and 2 and their phosphorylated forms were observed. Thus, progesterone administered after MPTP in mice protected dopaminergic neurons through modulation of neuroinflammation and BDNF. In humans, progesterone could possibly be used as a disease-modifying drug in prodromal Parkinson.
authors.affiliation: Neuroscience Research Unit, Centre Hospitalier Universitaire de Québec, CHUL, Quebec City, Canada; Faculty of Pharmacy, Laval University, Quebec City, Canada.
authors.forename: Nadhir
authors.initials: N
authors.lastname: Litim
authors.affiliation: Neuroscience Research Unit, Centre Hospitalier Universitaire de Québec, CHUL, Quebec City, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Morissette
authors.affiliation: Neuroscience Research Unit, Centre Hospitalier Universitaire de Québec, CHUL, Quebec City, Canada; Faculty of Pharmacy, Laval University, Quebec City, Canada. Electronic address: Therese.Dipaolo@crchul.ulaval.ca.
authors.forename: Thérèse
authors.initials: T
authors.lastname: Di Paolo
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020267:MPTP Poisoning / Q000378:metabolism* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D000066829:Neuroprotection; D018696:Neuroprotective Agents / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D050483:Dopamine Plasma Membrane Transport Proteins; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D050493:Vesicular Monoamine Transport Proteins; C528900:glial fibrillary astrocytic protein, mouse; D012701:Serotonin; D011374:Progesterone; D004298:Dopamine
keywords: BDNF; GFAP; Neuroinflammation; Parkinson's disease; Progesterone; Striatum